Analysis Tools|
Allele Symbol Allele Name Allele ID |
Tg(Cd4-cre)1Cwi transgene insertion 1, Christopher B Wilson MGI:2386448 |
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| Summary |
211 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in the thymus, spleen and liver
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• in the thymus, spleen and liver
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• naive CD4+ T cells show a marked decrease in the extent of store-operated Ca2+ entry after TCR stimulation with anti-CD3 antibody and ionomycin and after passive store depletion with thapsigargin
• upon TCR stimulation with anti-CD3 and anti-CD28 antibodies, naive CD4+ T cells show reduced induction of NFATc1 protein production (but no change in NFATc2 protein abundance), suggesting impaired activation of the Ca2+-NFAT pathway
• upon TCR stimulation with anti-CD3 antibody, naive CD4+ T cells show a marked reduction in the % of p-JNK+ cells, indicating impaired activation of the JNK signaling pathway
• naive CD4+ T cells stimulated with anti-CD3 antibody secrete significantly less IL-2 than similarly stimulated control cells
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• naive CD4+ T cells stimulated with anti-CD3 antibody secrete significantly less IL-2 than similarly stimulated control cells
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• naive CD4+ T cells show a marked decrease in the extent of store-operated Ca2+ entry after TCR stimulation with anti-CD3 antibody and ionomycin and after passive store depletion with thapsigargin
• upon TCR stimulation with anti-CD3 and anti-CD28 antibodies, naive CD4+ T cells show reduced induction of NFATc1 protein production (but no change in NFATc2 protein abundance), suggesting impaired activation of the Ca2+-NFAT pathway
• upon TCR stimulation with anti-CD3 antibody, naive CD4+ T cells show a marked reduction in the % of p-JNK+ cells, indicating impaired activation of the JNK signaling pathway
• naive CD4+ T cells stimulated with anti-CD3 antibody secrete significantly less IL-2 than similarly stimulated control cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice display anxiety-like behavior, showing reduced distance traveled, reduced distance in the center and much less time spend in the center of the open-field test
• however, mice exhibit normal extinction of fear memory in the continuous elevated plus-maze test
• treatment with BCX-1777, a purine nucleoside phosphorylase inhibitor, reduces anxiety symptoms
• mice treated with an adeno-associated virus expressing myelin basic protein promoter-driven Adora1 shRNA to knock-down the adenosine receptor A1 in oligodendrocytes rescues the anxiety phenotype
• treatment with 2-Deoxy-D-glucose, a glucose analog that inhibits its catabolic pathways, normalizes the anxiety-like symptoms
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• mice spend much less time in the center of the open-field test
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• CD4+ T cells exhibit reduced activities of oxidative phosphorylation and glycolysis
• naive CD4+ T cells have lower glycolysis but produce more M+5 ribulose-5-p, CAIR, adenosine, and inosine
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• various amino acids are upregulated in the serum, with highest increases in methionine, threonine, arginine, alanine, and proline
• however, levels of 5-HTP, serotonin, glutamate, and GABA are not affected
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• metabolites involved in purine metabolism are enriched in the serum, with most of the purines and their derivatives including adenine, hypoxanthine, and xanthine 10-100 times more abundant
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• xanthine levels are 10-100 times more abundant in serum
• treatment with BCX-1777 reduces serum xanthine levels
• depletion of CD4+ T cells with an anti-CD4 antibody decreases serum xanthine level
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| N |
• T cells do not show any obvious abnormalities in the development and homeostasis of T lymphocytes and mice show comparable sensitivities in models of experimental autoimmune encephalomyelitis as controls
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• CD4+ T cells exhibit reduced activities of oxidative phosphorylation and glycolysis
• naive CD4+ T cells have lower glycolysis but produce more M+5 ribulose-5-p, CAIR, adenosine, and inosine
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• xanthine levels are decreased in the peripheral immune organs
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• xanthine accumulates in the brain
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• left amygdala exhibits higher numbers of nonneuronal cells than the right amygdala or wild-type left amygdala
• amygdala shows an increase in the percentage of oligodendrocytes
• treatment with 2-Deoxy-D-glucose normalizes the pathological changes of the left amygdala
• depletion of CD4+ T cells with an anti-CD4 antibody decreases the oligodendrocyte percentage in the amygdala
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• left amygdala is enlarged
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• SOCE (store-operated Ca2+ entry) reduced by 3050% in naive CD4+ and CD8+ T cells after induction by depletion of ER Ca2+ stores with thapsigargin
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• SOCE (store-operated Ca2+ entry) reduced by 3050% in naive CD4+ and CD8+ T cells after induction by depletion of ER Ca2+ stores with thapsigargin
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 3- to 8-fold increase in IgM and IgG antibodies for single stranded DNA; however, this is 2- to 3-fold lower than in mice homozygous for Fastm1.1Cgn and mice do not display the increase in double negative T cells or lymphoproliferative disease seen in Faslpr homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutant thymocytes are resistant to Fas-induced apoptosis
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• mutant T cells have impaired early cell cycle transition
• mutant T cells exhibit a slower cell cycle kinetic and do not accumulate in culture due to cell death by necrosis during proliferation
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• mutant mice consistently possess elongated lymphnodes and spleen
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• an increase of TER-119+ red blood cells in the spleen but not in the bone marrow
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• a drastic increase of B cells in the lymph nodes and spleen
• absolute number of B cells is higher in mutant mice that exhibit splenomegaly
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• the percentage of T cells in the peripheral organs of mutant mice is reduced
• the absolute cell number of CD4+ and CD8+ T cells is equal to controls
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• mutant thymocytes are resistant to Fas-induced apoptosis
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• mutant T cells have impaired early cell cycle transition
• mutant T cells exhibit a slower cell cycle kinetic and do not accumulate in culture due to cell death by necrosis during proliferation
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• mutant mice consistently possess elongated lymphnodes and spleen
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• a drastic increase of B cells in the lymph nodes and spleen
• absolute number of B cells is higher in mutant mice that exhibit splenomegaly
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• the percentage of T cells in the peripheral organs of mutant mice is reduced
• the absolute cell number of CD4+ and CD8+ T cells is equal to controls
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• mutant mice consistently possess elongated lymphnodes and spleen
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• mutant mice are more susceptible to Toxoplasma gondii infection
• born at the expected Mendelian ratios and appear healthy with no gross abnormalities
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• mutant thymocytes are resistant to Fas-induced apoptosis
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• mutant T cells have impaired early cell cycle transition
• mutant T cells exhibit a slower cell cycle kinetic and do not accumulate in culture due to cell death by necrosis during proliferation
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• mutant thymocytes are resistant to Fas-induced apoptosis
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• mutant mice consistently possess elongated lymphnodes and spleen
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 75% of mice die between 10 and 18 months of age
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• loss of B and T cells is at least in part the result of increased apoptosis
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• thymus cell numbers decline from normal at 2 months of age to about 50% and 10% of control at 5 and 7 months of age, respectively
• occasionally complete thymic involution is seen at 7 months of age
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• treatment with a neutralizing Fasl antibody results in accumulation of Thy1+ B220+ CD4- CD8- cells similar to the phenotype of Faslpr homozygous mice
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• gradual decline in B cell numbers in secondary lymphoid organs beginning after 2 months of age resulting in almost complete lymphopenia in the lymph nodes
• treatment with a neutralizing Fasl antibody prevents loss of B cells from the inguinal lymph nodes
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• the fraction of activated/memory T cells in the spleen increases from nearly normal at 2 months of age to about 91% at 7 months of age
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• gradual decline in T cell numbers in secondary lymphoid organs beginning after 2 months of age resulting in almost complete lymphopenia in the lymph nodes
• treatment with a neutralizing Fasl antibody prevents loss of T cells from the inguinal lymph nodes
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• about 50% of peripheral T cell are activated at 5 months of age
• the fraction of activated/memory T cells in the spleen increases from nearly normal at 2 months of age to about 91% at 7 months of age
• these activated T cells express very high levels of FASL at 5 months of age
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• enlarged with disruption of the architecture, loss of white pulp, sclerosis , and hyalinization at 5 months of age
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• gradual decline in total cells, T cells, and B cells
• T cells and B cells are about 160% of control at 2 months, 60% of control at 5 months and 23% (T cells) and 44% (B cells) of control at 7 months
• widespread apoptosis is seen at 16 weeks of age
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• gradual decline in B and T cell numbers in secondary lymphoid organs beginning after 2 months of age resulting in almost complete lymphopenia in the lymph nodes
• loss of B and T cells is at least in part the result of increased apoptosis
• at 5 months of age in 6 of 8 mice inguinal lymph nodes contain fewer than 0.1 million cells and at 7 months in 4 of 4 mice inguinal lymph nodes are almost empty
• treatment with a neutralizing Fasl antibody prevents loss of B and T cells from the inguinal lymph nodes
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• 3- to 8-fold increase in IgM and IgG antibodies for single stranded DNA; however, this is 2- to 3-fold lower than in mice homozygous for Fastm1.1Cgn and mice do not display the increase in double negative T cells or lymphoproliferative disease seen in Faslpr homozygotes
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• mild to moderate inflammatory cell infiltration
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• mild to moderate inflammatory cell infiltration
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• lung disease begins with infiltration of T and B cells predominantly around the arteries and bronchi around 5 months of age and this is accompanied by high levels of apoptosis
• treatment with a neutralizing Fasl antibody prevents lymphocyte infiltration
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• intense alveolitis with infiltration of lymphocytes, neutrophils, and activated macrophages at 10 months of age
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• at 10 months of age, mice develop a severe wasting syndrome with loss of about 30% of their body weight
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• enlarged with disruption of the architecture, loss of white pulp, sclerosis , and hyalinization at 5 months of age
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• lung disease begins with infiltration of T and B cells predominantly around the arteries and bronchi around 5 months of age and this is accompanied by high levels of apoptosis
• treatment with a neutralizing Fasl antibody prevents lymphocyte infiltration
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• intense alveolitis with infiltration of lymphocytes, neutrophils, and activated macrophages at 10 months of age
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• at 10 months of age, mice develop severe inflammatory pulmonary fibrosis with massive accumulation of elastic fibers and intense alveolitis
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• mild to moderate inflammatory cell infiltration
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• mild to moderate inflammatory cell infiltration
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• loss of B and T cells is at least in part the result of increased apoptosis
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• thymus cell numbers decline from normal at 2 months of age to about 50% and 10% of control at 5 and 7 months of age, respectively
• occasionally complete thymic involution is seen at 7 months of age
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• enlarged with disruption of the architecture, loss of white pulp, sclerosis , and hyalinization at 5 months of age
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• treatment with a neutralizing Fasl antibody results in accumulation of Thy1+ B220+ CD4- CD8- cells similar to the phenotype of Faslpr homozygous mice
|
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• gradual decline in B cell numbers in secondary lymphoid organs beginning after 2 months of age resulting in almost complete lymphopenia in the lymph nodes
• treatment with a neutralizing Fasl antibody prevents loss of B cells from the inguinal lymph nodes
|
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• the fraction of activated/memory T cells in the spleen increases from nearly normal at 2 months of age to about 91% at 7 months of age
|
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• gradual decline in T cell numbers in secondary lymphoid organs beginning after 2 months of age resulting in almost complete lymphopenia in the lymph nodes
• treatment with a neutralizing Fasl antibody prevents loss of T cells from the inguinal lymph nodes
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• about 50% of peripheral T cell are activated at 5 months of age
• the fraction of activated/memory T cells in the spleen increases from nearly normal at 2 months of age to about 91% at 7 months of age
• these activated T cells express very high levels of FASL at 5 months of age
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• gradual decline in total cells, T cells, and B cells
• T cells and B cells are about 160% of control at 2 months, 60% of control at 5 months and 23% (T cells) and 44% (B cells) of control at 7 months
• widespread apoptosis is seen at 16 weeks of age
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• loss of B and T cells is at least in part the result of increased apoptosis
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• thymus cell numbers decline from normal at 2 months of age to about 50% and 10% of control at 5 and 7 months of age, respectively
• occasionally complete thymic involution is seen at 7 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• serum levels of T. muris-specific IgG1 are decreased compared to controls, IgG2a levels are increased, and total IgE is lower in infected mutants
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• under neutral and Th2 conditions, interferon gamma (Ifng)-producing cells increase in culture compared to controls; under Th1 conditions, there is no change in percentage of Ifng-producing cells
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• Th2 cell differentiation is impaired in culture compared to control CD4 trangenic mice
• under Th2 cell conditions, percentage of T cells expressing Il-4 is lower than in control cultures
• Th2 cytokine production is lower in mice after inoculation with T. muris (helminth)
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• mice are resistant to Leishmania major infection; parasitic replication is controlled and lesions are resolved compared to BALB/c controls
• lymph node cells produce abundant amounts of Ifng
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• mutants are unable to fight infection by T. muris, a helminthic pathogen
• Th2-dependent goblet cell and mucin responses are absent at day 21 after infection
• mice have a higher worm burden than control CD4 transgenic mice; at 32 days after inoculation, infection is still present
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• serum levels of T. muris-specific IgG1 are decreased compared to controls, IgG2a levels are increased, and total IgE is lower in infected mutants
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• under neutral and Th2 conditions, interferon gamma (Ifng)-producing cells increase in culture compared to controls; under Th1 conditions, there is no change in percentage of Ifng-producing cells
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• Th2 cell differentiation is impaired in culture compared to control CD4 trangenic mice
• under Th2 cell conditions, percentage of T cells expressing Il-4 is lower than in control cultures
• Th2 cytokine production is lower in mice after inoculation with T. muris (helminth)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no abnormal phenotype is observed in mice in which autoimmune encephalitis has not been induced
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• less proliferation in culture of splenocytes collected 21 days after induction of autoimmune encephalitis
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• increased proportion of regulatory T cells early in the course of experimental autoimmune encephalitis
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• decreased overall T cell accumulation during the course of experimental autoimmune encephalitis
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• autoimmune encephalitis induced by treatment with myelin oligodendrocyte glycoprotein peptide results in less severe disease than in controls
• time to initial symptoms similar to controls
• disease state is qualitatively similar to controls
• no mortality due to experimental autoimmune encephalitis
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• less proliferation in culture of splenocytes collected 21 days after induction of autoimmune encephalitis
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• increased proportion of regulatory T cells early in the course of experimental autoimmune encephalitis
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• decreased overall T cell accumulation during the course of experimental autoimmune encephalitis
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• less proliferation in culture of splenocytes collected 21 days after induction of autoimmune encephalitis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• 4-week-old mice show normal CD4+ and CD8+ T cell development and thymic negative selection
• 24-week-old mice do NOT exhibit spontaneous autoimmune symptoms and have normal serum levels of autoantibodies, including anti-ANA, anti-double stranded DNA (dsDNA), and rheumatoid factor (RF)
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• expression of Foxp3 (a Treg master transcription factor) is significantly decreased in T cells isolated from the spleen and lymph nodes; numbers of Foxp3+ T cells are decreased
• mRNA levels of Treg signature genes, such as Ctla4, Pdcd1 (Pd-1), Il10, and Il2ra (Cd25), are significantly decreased in T cells
• flow cytometry analyses confirm reduction of Treg markers CTLA4, IKZF2 (Helios), and IL2RA (CD25) and effector Treg markers (CD44 and CD62L) in T cells; however, CD25 protein levels in Treg (CD4+FOXP3+) cells are normal
• ratios of individual introns of Foxp3 pre-mRNA to Foxp3 mRNA levels are increased in in vitro differentiated Treg cells, suggesting reduced Foxp3 mRNA splicing
• reduction of FOXP3 protein levels in T cells is reversed by overexpression of DDX39B phosphomimetic (T389D) mutant protein in the absence of TGF-beta stimulation
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• upon TGF-beta stimulation, splenic CD4+ T cells isolated from 8-week-old mice show reduced in vitro differentiation into Treg cells (CD4+FOXP3+)
• however, in vitro differentiation of Th1, Th2, and Th17 is unaffected
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• 4-week-old mice show a significant reduction in the population of regulatory T cells (Treg, CD4+FOXP3+) in the spleen and lymph nodes but not in the thymus
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• in a co-culture assay, Treg cells from 8-week-old mice exhibit reduced suppressive function, failing to inhibit the proliferation of CFSE-labeled wild-type effector T cells
• however, TCR-induced T cell proliferation of effector T cells is normal
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• in the MOG-induced EAE model, the clinical score is relatively normal during the acute phase but remains high during the remission phase, unlike in wild-type controls; serum levels of proinflammatory cytokines (IL-17A, IL-6, and IFN-gamma) are significantly elevated whereas the level of anti-proinflammatory cytokine IL-10 is significantly decreased, and CNS-infiltrating and brain tissue levels of Treg cells are reduced whereas levels of infiltrating Th17 cells are increased, indicating sustained inflammation during EAE remission
• moreover, in vitro MOG-restimulated IL-17A, IL-6, and IFN-gamma production is increased in lymph node T cells isolated from MOG-immunized mice whereas IL-10 production is reduced
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• expression of Foxp3 (a Treg master transcription factor) is significantly decreased in T cells isolated from the spleen and lymph nodes; numbers of Foxp3+ T cells are decreased
• mRNA levels of Treg signature genes, such as Ctla4, Pdcd1 (Pd-1), Il10, and Il2ra (Cd25), are significantly decreased in T cells
• flow cytometry analyses confirm reduction of Treg markers CTLA4, IKZF2 (Helios), and IL2RA (CD25) and effector Treg markers (CD44 and CD62L) in T cells; however, CD25 protein levels in Treg (CD4+FOXP3+) cells are normal
• ratios of individual introns of Foxp3 pre-mRNA to Foxp3 mRNA levels are increased in in vitro differentiated Treg cells, suggesting reduced Foxp3 mRNA splicing
• reduction of FOXP3 protein levels in T cells is reversed by overexpression of DDX39B phosphomimetic (T389D) mutant protein in the absence of TGF-beta stimulation
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• upon TGF-beta stimulation, splenic CD4+ T cells isolated from 8-week-old mice show reduced in vitro differentiation into Treg cells (CD4+FOXP3+)
• however, in vitro differentiation of Th1, Th2, and Th17 is unaffected
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• 4-week-old mice show a significant reduction in the population of regulatory T cells (Treg, CD4+FOXP3+) in the spleen and lymph nodes but not in the thymus
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• in a co-culture assay, Treg cells from 8-week-old mice exhibit reduced suppressive function, failing to inhibit the proliferation of CFSE-labeled wild-type effector T cells
• however, TCR-induced T cell proliferation of effector T cells is normal
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• in the syngeneic KPC pancreatic cancer model, tumor-bearing mice established by s.c. injection of pancreatic cancer cells from KPC (Krastm4Tyj/Kras+ Trp53tm2Tyj/Trp53+ Tg(Pdx1-cre)6Tuv/0) mice and then i.p. injected with either anti-PD-1 antibody or IgG control antibody show a drastic reduction of tumor-infiltrating Treg (CD4+ FOXP3+) cells in tumor tissues; similarly, the % of CTLA4+ CD8+ (exhausted) cytotoxic T cells is also reduced in tumor tissues
• IHC assays show that DDX39B proteins are mainly localized in the cytoplasm of FOXP3+ T cells in tumor tissues from tumor-bearing mice, unlike in control mice where DDX39B proteins are largely localized in the nucleus
• in adoptive transfer experiments, recipient mice transferred with Treg cells also exhibit a decrease of tumor-infiltrating Treg cells and exhausted (CTLA-4+) CD8+ T cells in tumor tissues
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• in the syngeneic KPC pancreatic cancer model, tumor-bearing mice established by s.c. injection of pancreatic cancer cells from KPC mice and then i.p. injected with either anti-PD-1 antibody or IgG control antibody show a significant decrease in tumor volume relative to anti-IgG treated control mice
• adoptive transfer of Treg cells into irradiated recipient mice followed by injection of KPC tumor cells and treatment of tumor-bearing mice with anti-PD-1 antibody results in reduced tumor volumes relative to those in recipient mice transferred with wild-type Treg cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• frequencies of T cells
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• elevated numbers of immune cell populations at age >3 months
• elevated numbers of CD4+ and CD8+ T cells with CD44hiCD62Lhi memory and/or CD44hiCD62Llo effector phenotypes
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• CD19+ CD38- GL.7+ in spleen after lymphocytic choriomeningitis virus (LCMV) infection
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• decreased Foxp3+ cells in thymus, spleen and lymph nodes
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• severely compromised proliferation of CD4+ cells
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• reduced number in spleen after lymphocytic choriomeningitis virus (LCMV) infection
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• after lymphocytic choriomeningitis virus (LCMV) infection
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• SOCE (store-operated Ca2+ entry) completely abolished in naive CD4+ and CD8+ T cells after induction by depletion of ER Ca2+ stores with thapsigargin
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| N |
• IgM level after lymphocytic choriomeningitis virus (LCMV) infection
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• elevated numbers of immune cell populations at age >3 months
• elevated numbers of CD4+ and CD8+ T cells with CD44hiCD62Lhi memory and/or CD44hiCD62Llo effector phenotypes
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• CD19+ CD38- GL.7+ in spleen after lymphocytic choriomeningitis virus (LCMV) infection
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• decreased Foxp3+ cells in thymus, spleen and lymph nodes
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• severely compromised proliferation of CD4+ cells
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• reduced number in spleen after lymphocytic choriomeningitis virus (LCMV) infection
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• after lymphocytic choriomeningitis virus (LCMV) infection
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• SOCE (store-operated Ca2+ entry) completely abolished in naive CD4+ and CD8+ T cells after induction by depletion of ER Ca2+ stores with thapsigargin
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• elevated numbers of immune cell populations at age >3 months
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• elevated numbers of immune cell populations at age >3 months
• elevated numbers of CD4+ and CD8+ T cells with CD44hiCD62Lhi memory and/or CD44hiCD62Llo effector phenotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• ability to form large T cell aggregates after antigen re-stimulation is severely compromised
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• thymidine incorporation by CD4+ T cells after antigen re-stimulation is reduced by 50%
• decreased cell division
• defect in thymidine incorporation is rescued by addition of IL-2
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• cytokine production is reduced to 10-20% of control levels after antigen re-stimulation
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• ability to form large T cell aggregates after antigen re-stimulation is severely compromised
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• thymidine incorporation by CD4+ T cells after antigen re-stimulation is reduced by 50%
• decreased cell division
• defect in thymidine incorporation is rescued by addition of IL-2
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• thymidine incorporation by CD4+ T cells after antigen re-stimulation is reduced by 50%
• decreased cell division
• defect in thymidine incorporation is rescued by addition of IL-2
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• bone marrow cells transplanted in Ldlrtm1Her leads to large atherosclerotic lesions with expended fibrous caps and deviation toward TH17
• however, IL17A neutralization prevents fibrous cap expansion
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Plcg1tm1Rwen/Plcg1tm1Gcrp Tg(Cd4-cre)1Cwi/0 mice develop inflammatory/autoimmune disease
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• in the spleen and lymph nodes compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi mice
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• peripheral T cells are reduced compared to in wild-type mice
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• in the thymus and spleen compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi mice
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• mice exhibit an increase in T cell activation compared with wild-type mice
• however, activation phenotype is not cell intrinsic
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• mice exhibit a higher percentage of single positive T cells and splenic T cells than in wild-type mice
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• in symptomatic mice without an increase in anti-nuclear antibodies
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• in one third of mice
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• from 2 to 3 weeks
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• in female and male mice
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• in one third of mice
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• in the spleen and lymph nodes compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi mice
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• peripheral T cells are reduced compared to in wild-type mice
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• in the thymus and spleen compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi mice
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• mice exhibit an increase in T cell activation compared with wild-type mice
• however, activation phenotype is not cell intrinsic
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• mice exhibit a higher percentage of single positive T cells and splenic T cells than in wild-type mice
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• in one third of mice
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• mice exhibit a higher percentage of single positive T cells and splenic T cells than in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 N |
• these mice do not have the wasting autoimmune disease normally observed in mice with conditional deletion of Tgfbr2 in CD4+ T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
 N |
• these mice do not have the wasting autoimmune disease normally observed in mice with conditional deletion of Tgfbr2 in CD4+ T cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• double positive thymocyte differentiation is impaired compared to in control mice
• however, double positive thymocyte survival is normal
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• until 6 weeks of age, intermediate CD4+ CD8lo cells accumulate more slowly than in control mice
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• until 6 weeks of age, mature CD4+ cells accumulate more slowly than in control mice
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• CD4 single positive thymocytes exhibit abnormal mitotic figures with multiple spindles, chromosome segregation defects and poor survival compared with control cells
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• until 6 weeks of age, mature CD4+ cells accumulate more slowly than in control mice
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• decreased survival
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• double positive thymocyte differentiation is impaired compared to in control mice
• however, double positive thymocyte survival is normal
|
|
• until 6 weeks of age, intermediate CD4+ CD8lo cells accumulate more slowly than in control mice
|
|
• until 6 weeks of age, mature CD4+ cells accumulate more slowly than in control mice
|
|
• CD4 single positive thymocytes exhibit abnormal mitotic figures with multiple spindles, chromosome segregation defects and poor survival compared with control cells
|
|
• until 6 weeks of age, mature CD4+ cells accumulate more slowly than in control mice
|
|
• decreased survival
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit anxiety-like behavior, showing reduced distance traveled, reduced distance in the center and much less time spend in the center of the open field test
|
|
• mice spend much less time in the center of the open-field test
|
|
• CD4+ T cells exhibit reduced activities of oxidative phosphorylation and glycolysis
|
|
• CD4+ T cells exhibit reduced activities of oxidative phosphorylation and glycolysis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• type 17 differentiation of virus-specific CD8+ T cells is normal
|
|
• 8 and 30 days after LCMV infection, mice exhibit fewer antigen-specific CD8+ T cells in the spleen and other tissues compared with wild-type mice
|
|
• in CD8+ T cells of LCMV-infected mice and restimulated cells
|
|
• in CD8+ T cells of LCMV-infected mice and restimulated cells
|
|
• in CD8+ T cells of LCMV-infected mice and restimulated cells
|
|
• LCMV-infected mice exhibit decreased antigen-specific CD8+ T cells, increased viral load in the blood, and increased CD8+ T cell production of IL2, TNF, and IL17 compared with wild-type mice
|
|
• 8 and 30 days after LCMV infection, mice exhibit fewer antigen-specific CD8+ T cells in the spleen and other tissues compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not exhibit lymphocyte infiltration of organs and the number and function of T regulatory cells are normal
|
|
• peripheral T cells exhibit increased apoptosis compared to in wild-type mice
• apoptosis cannot be prevented by adding the blocking anti-FasL antibodies unlike in wild-type cultures
|
|
• progressively as mice age
|
|
• progressively as mice age
|
|
• nearly all T cells exhibit an activated phenotype in the absence of an overt antigen challenge unlike in wild-type mice
• following stimulation with anti-CD3 plus anti-CD28 antibodies or phorbol 12-myristate 13-acetate plus ionomycin, a higher percentage of CD4+ T cells produce IL-1 and CD8+ cells produce IL-2 and IFN-gamma compared to in treated wild-type mice
• T cells acquire the activated phenotype during the double positive to single positive thymocyte transition by a cell-autonomous mechanism
|
|
• peripheral T cells exhibit increased apoptosis compared to in wild-type mice
• apoptosis cannot be prevented by adding the blocking anti-FasL antibodies unlike in wild-type cultures
|
|
• progressively as mice age
|
|
• progressively as mice age
|
|
• nearly all T cells exhibit an activated phenotype in the absence of an overt antigen challenge unlike in wild-type mice
• following stimulation with anti-CD3 plus anti-CD28 antibodies or phorbol 12-myristate 13-acetate plus ionomycin, a higher percentage of CD4+ T cells produce IL-1 and CD8+ cells produce IL-2 and IFN-gamma compared to in treated wild-type mice
• T cells acquire the activated phenotype during the double positive to single positive thymocyte transition by a cell-autonomous mechanism
|
|
• peripheral T cells exhibit increased apoptosis compared to in wild-type mice
• apoptosis cannot be prevented by adding the blocking anti-FasL antibodies unlike in wild-type cultures
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 30 days after LCMV infection, mice exhibit fewer antigen-specific CD8+ T cells in the bone marrow compared with wild-type mice
|
|
• LCMV-infected mice exhibit decreased antigen-specific CD8+ T cells and increased viral load in the blood after 60 days compared with wild-type mice
|
|
• 30 days after LCMV infection, mice exhibit fewer antigen-specific CD8+ T cells in the bone marrow compared with wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased mature miR-150 in thymocytes, naive peripheral CD4+ T cells and Th2 cells with increased pre-miR-150 found in naive peripheral CD4+ and Th2 cells
• decreased mature miR-21 in thymocytes, Th1 and Th2 cells with increased pre-miR-21 found in Th1 and Th2
• decreased mature miR-103 and miR-29 in T cells but with no accumulation of their precursor polypeptides
|
|
• stimulation of Th1 or Th2 cells in culture causes increased apoptosis
|
|
• stimulation of Th1 or Th2 cells in culture yields slower proliferation than normal, decreased expansion and increased apoptotic and dead cells
|
| N |
• normal thymocyte number and subpopulations
|
|
• stimulation of Th1 or Th2 cells in culture causes increased apoptosis
|
|
• stimulation of Th1 or Th2 cells in culture yields slower proliferation than normal, decreased expansion and increased apoptotic and dead cells
|
|
• spleen and lymph nodes have fewer CD3+ cells with a decreased percentage (fourfold reduction in spleen) of CD8+ T cells and a smaller decrease (twofold reduction) in percentage of CD4+ T cells
|
|
• ThN cultures have increased IFNG expression leading to Th1 production
• cultured Th1 cells show accelerated loss of stimulation-induced IL2 expression
|
|
• Th2 cultures have 30% lower expression of Gata3 transcripts
• IFNG expression is not appropriately repressed in Th2 cultures
|
|
• stimulation of Th1 or Th2 cells in culture causes increased apoptosis
|
|
• stimulation of Th1 or Th2 cells in culture yields slower proliferation than normal, decreased expansion and increased apoptotic and dead cells
|
|
• spleen and lymph nodes have fewer CD3+ cells with a decreased percentage (fourfold reduction in spleen) of CD8+ T cells and a smaller decrease (twofold reduction) in percentage of CD4+ T cells
|
|
• ThN cultures have increased IFNG expression leading to Th1 production
• cultured Th1 cells show accelerated loss of stimulation-induced IL2 expression
|
|
• Th2 cultures have 30% lower expression of Gata3 transcripts
• IFNG expression is not appropriately repressed in Th2 cultures
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased mortality (40%) on days 5-8 post Listeria monocytogenes infection compared to controls
|
|
• no difference in serum TNF levels after LPS injection compared to wild-type, however serum TNF levels were decreased after liver injury
|
|
• increased resistance to liver injury after ConA-induced autoimmune hepatitis
|
|
• protected from S. aureus enterotoxin B induced toxic shock but no difference from wild-type after LPS challenge
|
|
• increased sensitivity to Listeria monocytogenes at high doses of infection, with elevated bacterial load on day 4 or 6 and increased mortality, although survivors were able to clear the bacteria by day 14
|
|
• no difference in serum TNF levels after LPS injection compared to wild-type, however serum TNF levels were decreased after liver injury
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• T cell receptor activation is highly repressed
• steady-state activation of T cells is normal
|
|
|
• T cell receptor activation is highly repressed
• steady-state activation of T cells is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• T cell receptor activation is highly repressed
• steady-state activation of T cells is normal
|
|
|
• T cell receptor activation is highly repressed
• steady-state activation of T cells is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls
• T cells exhibit decreased rolling velocity compared with control cells
|
|
• in the spleen
|
|
• in the lymph nodes and blood but not spleen
|
|
• in the blood and lymph nodes
|
|
• in the blood and lymph nodes
|
|
• T cells exhibit elevated chemotactic response to S1P and decreased response to CCL21 compared with control cells
• T cells exhibit defective entry into the lymph node compared with control cells
• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls
• T cells exhibit decreased rolling velocity compared with control cells
|
|
• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls
• T cells exhibit decreased rolling velocity compared with control cells
|
|
• in the spleen
|
|
• in the lymph nodes and blood but not spleen
|
|
• in the blood and lymph nodes
|
|
• in the blood and lymph nodes
|
|
• T cells exhibit elevated chemotactic response to S1P and decreased response to CCL21 compared with control cells
• T cells exhibit defective entry into the lymph node compared with control cells
• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls
• T cells exhibit decreased rolling velocity compared with control cells
|
|
• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls
• T cells exhibit decreased rolling velocity compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Th17 cells are absent in the lamina propia of these mice
|
|
• in vitro activation of CD4 T cells with IL-6 and IL-21 pushes differentiation towards a Th1 type instead of Th17 type
• Th17 cells are absent in the lamina propia of these mice
|
|
• a large proportion of CD4 T cells produce IFN-gamma when activated in vitro with IL-6 and IL-21
|
|
• IL-17 is not produced by CD4 T cells in response to in vitro activation with IL-6 or IL-21 plus TGF-beta
|
|
• in vitro activation of CD4 T cells with IL-6 and IL-21 pushes differentiation towards a Th1 type instead of Th17 type
• Th17 cells are absent in the lamina propia of these mice
|
|
• Th17 cells are absent in the lamina propia of these mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mature peripheral T reg cells are reduced in frequency
|
|
• mature peripheral T reg cells are reduced in frequency
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 94% reduction in cellularity
|
|
• slightly less apoptotic double positive T cells after 16 hours of culturing compared to transgenic mice that do not express Cre recombinase
|
|
• 93% reduction in number of double positive T cells
|
|
• 91% reduction in number single positive CD4 T cells
|
|
• 91% reduction in number single positive CD4 T cells
|
|
• 94% reduction in cellularity
|
|
• slightly less apoptotic double positive T cells after 16 hours of culturing compared to transgenic mice that do not express Cre recombinase
|
|
• 93% reduction in number of double positive T cells
|
|
• 91% reduction in number single positive CD4 T cells
|
|
• 91% reduction in number single positive CD4 T cells
|
|
• 94% reduction in cellularity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cellularity is reduced by 42%
|
|
• double positive T cells have attenuated TCR signaling as determined by reduced Ca flux and phosphorylation of downstream signaling proteins after TCR stimulation
|
|
• 2.5 fold increase in spleen weight to bodyweight ratio
|
|
• 1.9 fold increase in spleen cellularity
|
|
• 20 fold reduction in the percentage of double positive T cells that express surface markers associated with passage through the double positive stage
• slight increase in the number of apoptotic double positive T cells occurs after 16 hours in culture
|
|
• 45% reduction in the number of DN T cells in the thymus
|
|
• 43% reduction in the number of DP T cells in the thymus
|
|
• about a 5 fold increase in the number of dendritic cells found in the spleen
|
|
• 2-5 fold increase in the number of B cells in the spleen and lymph nodes
|
|
• about a 3.5 fold increase in the number of NK cells found in the spleen
|
|
• 2 to 5 fold reduction in the number of CD4 T cells in the spleen and lymph nodes
• 10 fold reduction in single positive CD4 T cells in the thymus
|
|
• 2 to 3 fold reduction in the number of CD8 T cells in the spleen and lymph nodes
• 10 fold reduction in single positive CD8 T cells in the thymus
|
|
• about a 3 fold increase in the number of gamma-delta T cells found in the spleen
|
|
• cellularity is reduced by 42%
|
|
• double positive T cells have attenuated TCR signaling as determined by reduced Ca flux and phosphorylation of downstream signaling proteins after TCR stimulation
|
|
• 2.5 fold increase in spleen weight to bodyweight ratio
|
|
• 1.9 fold increase in spleen cellularity
|
|
• 20 fold reduction in the percentage of double positive T cells that express surface markers associated with passage through the double positive stage
• slight increase in the number of apoptotic double positive T cells occurs after 16 hours in culture
|
|
• 45% reduction in the number of DN T cells in the thymus
|
|
• 43% reduction in the number of DP T cells in the thymus
|
|
• about a 5 fold increase in the number of dendritic cells found in the spleen
|
|
• 2-5 fold increase in the number of B cells in the spleen and lymph nodes
|
|
• about a 3.5 fold increase in the number of NK cells found in the spleen
|
|
• 2 to 5 fold reduction in the number of CD4 T cells in the spleen and lymph nodes
• 10 fold reduction in single positive CD4 T cells in the thymus
|
|
• 2 to 3 fold reduction in the number of CD8 T cells in the spleen and lymph nodes
• 10 fold reduction in single positive CD8 T cells in the thymus
|
|
• about a 3 fold increase in the number of gamma-delta T cells found in the spleen
|
|
• there are twice the number of cells within the mesenteric lymph nodes as compared to control mice
|
|
• cellularity is reduced by 42%
|
|
• double positive T cells have attenuated TCR signaling as determined by reduced Ca flux and phosphorylation of downstream signaling proteins after TCR stimulation
|
|
• 2.5 fold increase in spleen weight to bodyweight ratio
|
|
• 1.9 fold increase in spleen cellularity
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cellularity is reduced by 42%
|
|
• slight increase in the number of apoptotic double positive T cells after 16 hours of culturing, indicating apoptosis is occurring independent of TCR signaling
|
|
• 2.4 fold reduction in the number of DP T cells in thymus
|
|
• cellularity is reduced by 42%
|
|
• slight increase in the number of apoptotic double positive T cells after 16 hours of culturing, indicating apoptosis is occurring independent of TCR signaling
|
|
• 2.4 fold reduction in the number of DP T cells in thymus
|
|
• cellularity is reduced by 42%
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly increased Th1 cell numbers in spleen and pancreatic lymph nodes
|
|
• expansion of thymic and peripheral T reg cells
|
|
• significantly increased Th1 cell numbers in spleen and pancreatic lymph nodes
|
|
• expansion of thymic and peripheral T reg cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die at 3-4 weeks of age, before hyperglycemia is seen
|
|
• severe inflammatory infiltration of multiple organs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly increased Th1 cell numbers in spleen and pancreatic lymph nodes
|
|
• increased frequency of T reg in the thymus and pancreatic lymph nodes
• number of T reg cells in pancreatic lymph nodes is increased as well
|
|
• rapidly develop diabetes but with a low incidence
• slow kinetics of disease progression
|
|
• significantly increased Th1 cell numbers in spleen and pancreatic lymph nodes
|
|
• increased frequency of T reg in the thymus and pancreatic lymph nodes
• number of T reg cells in pancreatic lymph nodes is increased as well
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• improved survival
|
| N |
• do not develop diabetes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• improved survival
|
| N |
• absolute numbers of Th1 cells in the spleen is unchanged from controls
|
|
• significant reduction in spleen and pancreas
• reduced peripheral cell numbers
|
|
• percentage in pancreatic lymph nodes is increased
|
|
• total cellularity of the spleen is reduced in 3 week old diabetic mice
|
|
• total cellularity of pancreatic lymph nodes is reduced in 3 week old diabetic mice
|
|
• massive infiltration of leukocytes into Islets before diabetes develops
|
|
• in pancreatic T cells
|
|
• decreased Il22 expression in pancreatic T cells
|
|
• decreased Il17a in pancreatic T cells
|
|
• in pancreatic T cells
|
|
• in pancreatic T cells
|
|
• in pancreatic T cells
|
|
• become diabetic between 14 and 21 days of age
|
|
• massive infiltration of leukocytes into Islets before diabetes develops
|
|
• significant reduction in spleen and pancreas
• reduced peripheral cell numbers
|
|
• percentage in pancreatic lymph nodes is increased
|
|
• total cellularity of the spleen is reduced in 3 week old diabetic mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice have predominance of CD4+CD8- T cells in thymus and periphery, indicating that MHC I-restricted cells are forced to differentiate into CD4+CD8- T cells
|
|
• after TCR stimulation, interferon gamma production is absent from class I-restricted CD4+CD8- cells
|
|
• mice have predominance of CD4+CD8- T cells in thymus and periphery, indicating that MHC I-restricted cells are forced to differentiate into CD4+CD8- T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit the same phenotype as Cd4tm3.2Litt homozygotes
|
|
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
|
|
• mice exhibit a decreased in CD4 expression in lamina propria lin-c-kit+CD127+ cells compared to in wild-type mice
|
|
• in the thymus and spleen
|
|
• mice exhibit the same phenotype as Cd4tm3.2Litt homozygotes
|
|
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
|
|
• mice exhibit a decreased in CD4 expression in lamina propria lin-c-kit+CD127+ cells compared to in wild-type mice
|
|
• in the thymus and spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike in Fbxw7tm1Kei/Fbxw7tm1Kei Tg(CD4-cre)1Cwi mice, the number of double positive thymocytes is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mutants die by 11th day after T. gondii infection
|
|
• mucosa showed massive hyperplasia and infiltration with inflammatory cells and ectatic lymphatic vessels
|
|
• multifocal mucosal necroses resulted in numerous ulcerations
|
|
• all mutants developed prolapse under standard conditions, 9/15 mutants exhibited prolapse under pathogen free conditions
|
|
• incidence of bowel disease increased with age, reaching 33% at 6 months
• multifocal severe inflammation affected all strata of the colonic wall
|
|
• incidence of bowel disease increased with age, reaching 33% at 6 months
• multifocal severe inflammation affected all strata of the colonic wall
|
|
• expansion of lymph vessels in the intestine
|
|
• displayed a twofold increase in ear thickness after contact with allergen 2,4-dinitrochlorobenzene (DNCB) compared to controls, however innate inflammatory response and response to LPS were normal
|
|
• increased secretion of proinflammatory cytokines, TNF-alpha, IL-6, IL-12 and MCP-1 by stimulated splenocytes
|
|
• severe hepatitis seen after T. gondii infection
|
|
• T. gondii infection resulted in severe hepatitis and death by the 11th day after infection in mutants but not controls
|
|
• severe hepatitis seen after T. gondii infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit a normal response to LPS injection and T. muris infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells are decreased in the liver compared to in wild-type mice
|
|
• NK1.1-/CD44- stage 1 through 3 cells are decreased compared to in wild-type mice
• invariant NK T cell numbers in peripheral tissues (spleen, blood, and liver) is severely decreased compared to in wild-type mice
|
|
• CD8+ thymocytes exhibit reduced surface expression of CD8 compared to in wild-type mice
|
|
• T cells are decreased in the liver compared to in wild-type mice
|
|
• NK1.1-/CD44- stage 1 through 3 cells are decreased compared to in wild-type mice
• invariant NK T cell numbers in peripheral tissues (spleen, blood, and liver) is severely decreased compared to in wild-type mice
|
|
• CD8+ thymocytes exhibit reduced surface expression of CD8 compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number and percent of double positive thymocytes is increased compared to in wild-type mice but not as much as in Fbxw7tm1Kei/Fbxw7tm1Kei Tg(Lck-cre)1Cwi mice
|
|
• the number and percent of double positive thymocytes is increased compared to in wild-type mice but not as much as in Fbxw7tm1Kei/Fbxw7tm1Kei Tg(Lck-cre)1Cwi mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• nave T cells fail to differentiate into the Th2 sub-type when co-cultured with LPS-treated DC from Myd88-null mice
• addition of IL-4 rescued this defect
|
|
• nave T cells fail to differentiate into the Th2 sub-type when co-cultured with LPS-treated DC from Myd88-null mice
• addition of IL-4 rescued this defect
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• striking decrease on peripheral CD3 T cells
|
|
• dramatic 80% reduction of CD4+ thymocytes
• dramatic 50% reduction of CD8+ thymocytes
• surviving cells represent cells in which cre excision is incomplete
|
|
• dramatic 80% reduction of CD4+ thymocytes
|
|
• dramatic 50% reduction of CD8+ thymocytes
|
|
• striking decrease on peripheral CD3 T cells
|
|
• dramatic 80% reduction of CD4+ thymocytes
• dramatic 50% reduction of CD8+ thymocytes
• surviving cells represent cells in which cre excision is incomplete
|
|
• dramatic 80% reduction of CD4+ thymocytes
|
|
• dramatic 50% reduction of CD8+ thymocytes
|
|
• dramatic 80% reduction of CD4+ thymocytes
• dramatic 50% reduction of CD8+ thymocytes
• surviving cells represent cells in which cre excision is incomplete
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slight decrease in proliferative response following stimulation of CD4+ T cells
|
|
• number of IL10 producing Th2 cells is increased from 16% to 38%
• however, differentiation of Th1 and Th17 cells is similar to wild-type
|
|
• increase in IL10 expression in naive CD4 T cells following stimulation with PMA and ionomycin
• number of IL10 producing Th2 cells is increased from 16% to 38%
|
|
• slight increase in IL4 expression in naive CD4 T cells following stimulation with PMA and ionomycin
|
|
• slight decrease in proliferative response following stimulation of CD4+ T cells
|
|
• number of IL10 producing Th2 cells is increased from 16% to 38%
• however, differentiation of Th1 and Th17 cells is similar to wild-type
|
|
• slight decrease in proliferative response following stimulation of CD4+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD4 silencing is defective in these mice leading to expression of CD4 on cytotoxic T cells that normally only express CD8
• these peripheral double positive T cells have the cytotoxic effector functions of CD8+ T cells
|
|
• all peripheral CD8+ T cells co-express CD4 leading to a large increase in double positive numbers in the spleen
|
|
• CD4 silencing is defective in these mice leading to expression of CD4 on cytotoxic T cells that normally only express CD8
• these peripheral double positive T cells have the cytotoxic effector functions of CD8+ T cells
|
|
• all peripheral CD8+ T cells co-express CD4 leading to a large increase in double positive numbers in the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• very few CD8 T cells found in the thymus
• the CD8 T cells that found have escaped Cre excession
|
|
• very few CD8 T cells found in the thymus
• the CD8 T cells that found have escaped Cre excession
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• slight reduction in number of mature T cells in the thymus
• Cbfbeta protein is detectable in T cells of the thymus but not the periphery
|
|
• significant levels of the Th-2 cytokine IL-4 are produced when nave T cells are activated in vitro
• some T cells produce both IL-4 and IFN-gamma when nave T cells are cultured under Th1 polarizing conditions
|
|
• in the spleen
|
|
• vast majority of CD8-positive T cells in the periphery also express CD4
(J:125953)
• CD8+ T cells exhibit a de-repression of CD4 expression unlike in wild-type mice
(J:158962)
|
|
• reduced number of single positive CD8 T cells
|
|
• in the thymus and spleen
|
|
• at least 10 fold higher levels in the serum
|
|
• at least 10 fold higher levels in the serum
|
|
• at least 10 fold higher levels of IgG1 in the serum
|
|
• an asthma-like disease occurs with lymphocytes and eosinophils infiltrating the bronchioles, perivascular space, and the alveolar septae
|
|
• slight reduction in number of mature T cells in the thymus
• Cbfbeta protein is detectable in T cells of the thymus but not the periphery
|
|
• significant levels of the Th-2 cytokine IL-4 are produced when nave T cells are activated in vitro
• some T cells produce both IL-4 and IFN-gamma when nave T cells are cultured under Th1 polarizing conditions
|
|
• in the spleen
|
|
• vast majority of CD8-positive T cells in the periphery also express CD4
(J:125953)
• CD8+ T cells exhibit a de-repression of CD4 expression unlike in wild-type mice
(J:158962)
|
|
• reduced number of single positive CD8 T cells
|
|
• in the thymus and spleen
|
|
• at least 10 fold higher levels in the serum
|
|
• at least 10 fold higher levels in the serum
|
|
• at least 10 fold higher levels of IgG1 in the serum
|
|
• an asthma-like disease occurs with lymphocytes and eosinophils infiltrating the bronchioles, perivascular space, and the alveolar septae
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite the reduction in CD4+ and CD8+ T cells, the pool of memory T cells is normal
|
|
• CD8+ cells exhibit an immature phenotype due to incomplete thymic maturation
|
|
• T cells exhibit incomplete repertoires of TCR specificities with a biased Vbeta chain usage unlike in wild-type cells
|
|
• the naive T cell population in the peripheral pool is depleted and mice remain lymphopenic over time
|
|
• by 50%
|
|
• CD4+ cells in the thymus are almost completely absent
• fewer CD4+ and CD8+ cells are found in the lymph, nodes, spleen and blood compared to in wild-type mice with remaining cells accounted for by incomplete recombination
|
|
• fewer immature CD8+ T cells are found in the thymus compared to in wild-type mice
• fewer CD4+ and CD8+ cells are found in the lymph, nodes, spleen and blood compared to in wild-type mice with remaining cells accounted for by incomplete recombination
|
|
• mice exhibit a loss of CD4+ NK T cells in the liver compared to in wild-type mice
|
|
• the spleen has a smaller T cell zone than in wild-type mice
• however, overall architecture is normal
|
|
• following infection with N. brasiliensis, CD4+ T cells preferentially differentiate towards Th1 and Th17 cells unlike similarly treated wild-type mice whose CD4+ T cells preferentially differentiate towards Th2 cells
|
|
• the lymph nodes have smaller T cell zones than in wild-type mice
• however, overall architecture is normal
|
|
• mice infected with N. brasiliensis exhibit impaired effector cell recruitment and worm expulsion with 4-fold higher worm counts in the small intestine compared to in similarly treated wild-type mice
• nine days after infection with N. brasiliensis, mice exhibit reduced basophil and eosinophil frequencies in the blood and lungs compared to similarly treated wild-type mice
• after infection with N. brasiliensis, total numbers of eosinophils, basophils and CD4+ T cells in the lungs are 5- to 10-fold lower than in similarly treated wild-type mice
• following infection with N. brasiliensis, CD4+ T cells preferentially differentiate towards Th1 and Th17 cells unlike similarly treated wild-type mice whose CD4+ T cells preferentially differentiate towards Th2 cells
• however, IgE levels in mice infected with N. brasiliensis are normal
|
|
• CD8+ cells exhibit an immature phenotype due to incomplete thymic maturation
|
|
• T cells exhibit incomplete repertoires of TCR specificities with a biased Vbeta chain usage unlike in wild-type cells
|
|
• the naive T cell population in the peripheral pool is depleted and mice remain lymphopenic over time
|
|
• by 50%
|
|
• CD4+ cells in the thymus are almost completely absent
• fewer CD4+ and CD8+ cells are found in the lymph, nodes, spleen and blood compared to in wild-type mice with remaining cells accounted for by incomplete recombination
|
|
• fewer immature CD8+ T cells are found in the thymus compared to in wild-type mice
• fewer CD4+ and CD8+ cells are found in the lymph, nodes, spleen and blood compared to in wild-type mice with remaining cells accounted for by incomplete recombination
|
|
• mice exhibit a loss of CD4+ NK T cells in the liver compared to in wild-type mice
|
|
• the spleen has a smaller T cell zone than in wild-type mice
• however, overall architecture is normal
|
|
• following infection with N. brasiliensis, CD4+ T cells preferentially differentiate towards Th1 and Th17 cells unlike similarly treated wild-type mice whose CD4+ T cells preferentially differentiate towards Th2 cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• subset of CD8-positive T cells in the periphery also express intermediate levels of CD4
|
|
• very few CD8-positive T cells are found in the thymus
• level of mature CD8-postive T cells in the thymus reduced by 25%
|
|
• CD8+ T cell absolute numbers are decreased
|
|
• slighlty higher levels in the serum
|
|
• a mild asthma-like disease occurs in one third of the mice with lymphocytes and eosinophils infiltrating the bronchioles and perivascular space
|
|
• a mild asthma-like disease occurs in one third of the mice with lymphocytes and eosinophils infiltrating the bronchioles and perivascular space
|
|
• subset of CD8-positive T cells in the periphery also express intermediate levels of CD4
|
|
• very few CD8-positive T cells are found in the thymus
• level of mature CD8-postive T cells in the thymus reduced by 25%
|
|
• CD8+ T cell absolute numbers are decreased
|
|
• slighlty higher levels in the serum
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Enlarged spleen in Gt(ROSA)26Sortm1(ITK/SYK)Jrld/Gt(ROSA)26Sor+ Tg(Cd4-cre)1Cwi/0 mice
|
• mice die by 30 weeks
|
| N |
• mice exhibit normal B cell morphology
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• mice exhibit profound T cell lymphoproliferative disorder unlike wild-type mice
|
|
• mice exhibit a decrease in mature peripheral T cells compared with wild-type mice
|
|
• at 20 weeks, spleens exhibit infiltration of medium to large-sized lymphoid cells with irregular nuclei, prominent nucleoli, and high mitotic rates suggesting neoplastic growth unlike in wild-type mice
|
|
• at 20 weeks
|
|
• the majority of CD4+ and CD8+ T cells exhibit an activated phenotype unlike wild-type cells
|
|
• in remaining T cells
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• at 12 weeks
|
|
• at 12 weeks
|
|
• at 20 weeks
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• mice exhibit profound T cell lymphoproliferative disorder unlike wild-type mice
|
|
• mice exhibit a decrease in mature peripheral T cells compared with wild-type mice
|
|
• at 20 weeks, spleens exhibit infiltration of medium to large-sized lymphoid cells with irregular nuclei, prominent nucleoli, and high mitotic rates suggesting neoplastic growth unlike in wild-type mice
|
|
• at 20 weeks
|
|
• the majority of CD4+ and CD8+ T cells exhibit an activated phenotype unlike wild-type cells
|
|
• in remaining T cells
|
|
• mice develop highly proliferative populations of T cells in the bone marrow with infiltration into solid organs, including kidneys, livers, and lungs, unlike in wild-type mice
|
|
• in remaining T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced level of mature CD4-positive T cells in thymus
|
|
• reduced level of mature CD8-postive T cells in the thymus
|
|
• lower expression of TCRbeta
|
|
• severely reduced numbers in the spleen and lymph nodes resulting from decreased survival
|
|
• reduced level of mature CD4-positive T cells in thymus
|
|
• reduced level of mature CD8-postive T cells in the thymus
|
|
• lower expression of TCRbeta
|
|
• severely reduced numbers in the spleen and lymph nodes resulting from decreased survival
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly lower than in controls
|
|
• significantly lower than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• numbers are lower than in controls
|
|
• mice show a marked reduction in CD8+ T cells
|
|
• numbers are lower than in controls
|
|
• mice show a marked reduction in CD8+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly lower than in controls
|
|
• significantly lower than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significantly lower than in controls
|
|
• lower than in controls
|
|
• significantly lower than in controls
|
|
• lower than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
Reduced tumor growth in Fostm7Wag/Fostm7Wag Tg(Cd4-cre)1Cwi/0 mice following carcinoma cell inoculation
|
• following inoculation with Lewis lung carcinoma
|
|
• decreased lung tumor number and growth following inoculation with Lewis lung carcinoma or B16-F10 melanoma
|
|
• in the thymus
|
|
• in tumor cells following inoculation with Lewis lung carcinoma
|
|
• in tumor cells following inoculation with Lewis lung carcinoma
|
|
• in the thymus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number and percent of double positive thymocytes is increased compared to in wild-type mice
|
|
• the number and percent of double positive thymocytes is increased compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 7-fold following immunization with NP-KLH
• following immunization with SRBCs (sheep red blood cells)
|
|
• modestly in the spleen without altering lymph node numbers
|
|
• modestly in the spleen without altering lymph node numbers
• slightly in B cell follicles
• significantly in PNA+ IgD- germinal center areas
|
|
• following immunization with NP-KLH of SRBCs (sheep red blood cells)
|
|
• modestly in the spleen without altering lymph node numbers
|
|
• following immunization with NP-KLH, the ratio of germinal centers per B cell follicle is reduced compared to in similarly treated wild-type mice
|
|
• following immunization with SRBCs (sheep red blood cells)
|
|
• following immunization and a later antigen boost, mice exhibit defective immunological memory compared with wild-type mice
|
|
• following immunization with NP33-BSA, the NP-specific IgG1 titers are decreased compared to in similarly treated wild-type mice
• following immunization with NP3-BSA, high-affinity NP-specific IgG1 response is severely impaired compared to in similarly treated wild-type mice
• fewer IgG1-secreting antibody forming cells are detected in the spleen and bone marrow compared to in wild-type mice
|
|
• 7-fold following immunization with NP-KLH
• following immunization with SRBCs (sheep red blood cells)
|
|
• modestly in the spleen without altering lymph node numbers
|
|
• modestly in the spleen without altering lymph node numbers
• slightly in B cell follicles
• significantly in PNA+ IgD- germinal center areas
|
|
• following immunization with NP-KLH of SRBCs (sheep red blood cells)
|
|
• modestly in the spleen without altering lymph node numbers
|
|
• following immunization with NP-KLH, the ratio of germinal centers per B cell follicle is reduced compared to in similarly treated wild-type mice
|
|
• following immunization with SRBCs (sheep red blood cells)
|
|
• following immunization with NP33-BSA, the NP-specific IgG1 titers are decreased compared to in similarly treated wild-type mice
• following immunization with NP3-BSA, high-affinity NP-specific IgG1 response is severely impaired compared to in similarly treated wild-type mice
• fewer IgG1-secreting antibody forming cells are detected in the spleen and bone marrow compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit the same phenotype as Cd4tm3.2Litt homozygotes
|
|
• in the thymus
|
|
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
|
|
• the percentage of CD4 single positive cell in the thymus and spleen is decreased compared to in wild-type mice
|
|
• the percentage of CD8 single positive cell in the thymus and spleen is increased compared to in wild-type mice
|
|
• mice exhibit the same phenotype as Cd4tm3.2Litt homozygotes
|
|
• in the thymus
|
|
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
|
|
• the percentage of CD4 single positive cell in the thymus and spleen is decreased compared to in wild-type mice
|
|
• the percentage of CD8 single positive cell in the thymus and spleen is increased compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cachexic animals become moribund rapidly and are euthanized; by 6 months, 50% mortality in mutants is observed
|
|
• moribund animals show complete loss of visceral adipose tissue
|
| N |
• spleen and lymph nodes are not larger than controls despite T cell abnormalities
|
|
• higher frequency of granulocytes in spleen and lymph nodes is observed
|
|
• increase is detected in spleen and lymph nodes
|
|
• significant increase in frequency of activated (CD62Llo44hi) CD4+ T cells is observed in spleen and lymph nodes
|
|
• T lymphopenia in CD8+ compartment is observed
|
|
• total thymocyte number is decreased compared to controls at 6 weeks; reduced frequency of TCRbeta+ thymocytes with downregulated CD14 and CD69 is observed
• absolute number of mature thymocytes is significantly reduced
|
|
• absolute number of double positive (DP) thymocytes is significantly reduced compared to controls at 6 weeks
|
|
• significant reduction in frequency of mature CD8+ T cells is observed in periphery at 6 weeks
|
|
• mature peripheral T reg cells are reduced in frequency
|
|
• very high frequencies of interferon gamma- or IL-17A-secreting cells are observed; high frequency of interferon gamma/IL-17A double secreting cells is detected in moribund animals
• slight increase in frequency of interferon gamma- or IL-17A-secreting CD4+ T cells can be seen at 3 months
• regulatory T cells have reduced suppressive activity compared to controls; in vitro proliferation of stimulated CD25-CD4+ T cells is only partially suppressed
• deficient CD4+ T cells are capable of differentiating into Th1 or Th2 cells
|
|
• small foci of inflammatory cells are more prevalent than in controls
|
|
• infiltrating cells accumulate around most blood vessels in liver with additional foci in sinusoids
|
|
• infiltrating cells accumulate primarily around blood vessels, resulting in epithelial thickening of surrounding tissue
|
|
• higher frequency of granulocytes in spleen and lymph nodes is observed
|
|
• increase is detected in spleen and lymph nodes
|
|
• significant increase in frequency of activated (CD62Llo44hi) CD4+ T cells is observed in spleen and lymph nodes
|
|
• T lymphopenia in CD8+ compartment is observed
|
|
• total thymocyte number is decreased compared to controls at 6 weeks; reduced frequency of TCRbeta+ thymocytes with downregulated CD14 and CD69 is observed
• absolute number of mature thymocytes is significantly reduced
|
|
• absolute number of double positive (DP) thymocytes is significantly reduced compared to controls at 6 weeks
|
|
• significant reduction in frequency of mature CD8+ T cells is observed in periphery at 6 weeks
|
|
• mature peripheral T reg cells are reduced in frequency
|
|
• moribund animals show complete loss of visceral adipose tissue
|
|
• infiltrating cells accumulate around most blood vessels in liver with additional foci in sinusoids
|
|
• infiltrating cells accumulate primarily around blood vessels, resulting in epithelial thickening of surrounding tissue
|
|
• moribund animals exhibit reduction in muscle mass
|
|
• small foci of inflammatory cells are more prevalent than in controls
|
|
• total thymocyte number is decreased compared to controls at 6 weeks; reduced frequency of TCRbeta+ thymocytes with downregulated CD14 and CD69 is observed
• absolute number of mature thymocytes is significantly reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a population of CD4lo8+ double positive T cells in the mature thymocyte compartment and the spleen unlike in wild-type mice
|
|
• in the thymus
|
|
• in the spleen
|
|
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
|
|
• the percentage of CD4 single positive cell in the thymus and spleen is decreased compared to in wild-type mice
|
|
• the percentage of CD8 single positive cell in the thymus and spleen is increased compared to in wild-type mice
|
|
• mice exhibit a population of CD4lo8+ double positive T cells in the mature thymocyte compartment and the spleen unlike in wild-type mice
|
|
• in the thymus
|
|
• in the spleen
|
|
• the ratio of CD4 single positive to CD8 single positive T cells is inverted compared to in wild-type mice
|
|
• the percentage of CD4 single positive cell in the thymus and spleen is decreased compared to in wild-type mice
|
|
• the percentage of CD8 single positive cell in the thymus and spleen is increased compared to in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• similar to mice with recombination only in T cells
|
|
• similar to mice with recombination only in T cells
|
|
• similar to mice with recombination only in T cells
|
|
• similar to mice with recombination only in T cells
|
|
• similar to mice with recombination only in T cells
|
|
• similar to mice with recombination only in T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• regulatory T cells fail to drive Th17 differentiation
|
|
• regulatory T cells fail to drive Th17 differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• mice exhibit normal hemograms and response to thromogenesis
|
|
N |
• mice exhibit normal prothrombin tine and activated partial thromboplastin time
|
|
N |
• Igs levels are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• the number of CD44+CD25- DN1 cells is increased
|
|
|
• the number of CD44+CD25- DN1 cells is increased
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells exhibit an increase in migration towards CCL19 compared with control cells
|
|
• CD4+ T cells re-stimulated with anti-CD3 exhibit decreased production of Th1-associated cytokines compared with control cells
|
|
• CD4+ T cells re-stimulated with anti-CD3 exhibit increased production of Th2-associated cytokines compared with control cells
|
|
• in CD4+ T cells re-stimulated with anti-CD3
|
|
• in CD4+ T cells re-stimulated with anti-CD3
|
|
• in CD4+ T cells re-stimulated with anti-CD3
|
|
• in CD4+ T cells re-stimulated with anti-CD3
|
|
• in CD4+ T cells re-stimulated with anti-CD3
|
|
• T cells exhibit an increase in migration towards CCL19 compared with control cells
|
|
• CD4+ T cells re-stimulated with anti-CD3 exhibit decreased production of Th1-associated cytokines compared with control cells
|
|
• CD4+ T cells re-stimulated with anti-CD3 exhibit increased production of Th2-associated cytokines compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells hyper-proliferate in response to anti-CD3 and anti-CD28 stimulation
|
|
• thymocytes hyper-proliferate in response to anti-CD3 and anti-CD28 stimulation
|
|
• thymocytes and T cells secrete more IL-2 after activation relative to controls
|
|
• increased levels of rheumatoid factor are detected in the sera of older mice
|
|
• increased levels of anti-DNA antibodies are detected in the sera of older mice
|
|
• increased levels of anti-histone antibodies are detected in the sera of older mice
|
|
• T cells hyper-proliferate in response to anti-CD3 and anti-CD28 stimulation
|
|
• thymocytes hyper-proliferate in response to anti-CD3 and anti-CD28 stimulation
|
|
• thymocytes hyper-proliferate in response to anti-CD3 and anti-CD28 stimulation
|
|
• T cells hyper-proliferate in response to anti-CD3 and anti-CD28 stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
N |
• mice exhibit normal hemograms and response to thromogenesis
|
|
N |
• mice exhibit normal prothrombin tine and activated partial thromboplastin time
|
|
N |
• Igs levels are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• no defects in T cell development in the thymus, spleen, or lymph nodes are dectected
• no alteration in cell viability, expression of cell surface activation markers, cell cycle progression, or cell size
|
|
• inhibited anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
• enhanced differentiation in vitro
|
|
• inhibited anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
• increased inflammatory CD4+T cells and decreased FoxP3+CD4+T cells in the nervous system
|
|
• inhibited anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
• enhanced differentiation in vitro
|
|
• inhibited anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cellularity of the thymus is reduced by 17%
|
|
• double positive cell proportion is similar to controls but absolute numbers are reduced by 17%
|
|
• CD4+ cell numbers are reduced
|
|
• CD8+ cell numbers are increased
|
|
• cellularity of the thymus is reduced by 17%
|
|
• double positive cell proportion is similar to controls but absolute numbers are reduced by 17%
|
|
• CD4+ cell numbers are reduced
|
|
• CD8+ cell numbers are increased
|
|
• cellularity of the thymus is reduced by 17%
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after 3-day priming iunder Th2 conditions and restimulation for 4 hours, an ~19% decrease in percentage of Il4-producing cells is seen compared to controls
|
|
• ratio of CD4 single positive to CD8 single positive thymocytes is slightly reduced
|
|
• after infection with Schistosoma mansonii, 6-8 weeks later fewer lymph node cells make Il4 compared to controls
• after schistosoma egg antigen (SEA) stimulation for 5 days, ~3-fold fewer cells make Il4; production of other Th2 cytokines is reduced ~3-fold compared to control levels
|
|
• after 3-day priming iunder Th2 conditions and restimulation for 4 hours, an ~19% decrease in percentage of Il4-producing cells is seen compared to controls
|
|
• ratio of CD4 single positive to CD8 single positive thymocytes is slightly reduced
|
|
• after infection with Schistosoma mansonii, 6-8 weeks later fewer lymph node cells make Il4 compared to controls
• after schistosoma egg antigen (SEA) stimulation for 5 days, ~3-fold fewer cells make Il4; production of other Th2 cytokines is reduced ~3-fold compared to control levels
|
|
• after 3-day priming iunder Th2 conditions and restimulation for 4 hours, an ~19% decrease in percentage of Il4-producing cells is seen compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• when mutant bone marrow cells are transferred to mice lacking surface expression of MHC I, the single positive T cell population in the thymus is composed of small numbers of CD8+ T cells instead of large numbers of CD4+ T cells
|
|
• substantially decreased numbers of CD4+ single positive cells but normal numbers of CD8+ single positive cells
• CD4+ cells found in the lymph nodes had an activated or memory-like phenotype
|
|
• the number of TCRhi CD4 thymocytes is much smaller (0.2 x 106) than in their wild-type counterparts (10.9 x 106)
• the number of CD4 T cells found in the periphery is very small and all have a memory phenotype suggesting they are descendents of an even smaller progenitor pool
• CD4 T cells are virtually absent in the spleen of 1 week old mice, giving further evidence that CD4 T cell population in adults results from expansion of a small progenitor pool
|
|
• in stimulated T cells
|
|
• when mutant bone marrow cells are transferred to mice lacking surface expression of MHC I, the single positive T cell population in the thymus is composed of small numbers of CD8+ T cells instead of large numbers of CD4+ T cells
|
|
• substantially decreased numbers of CD4+ single positive cells but normal numbers of CD8+ single positive cells
• CD4+ cells found in the lymph nodes had an activated or memory-like phenotype
|
|
• the number of TCRhi CD4 thymocytes is much smaller (0.2 x 106) than in their wild-type counterparts (10.9 x 106)
• the number of CD4 T cells found in the periphery is very small and all have a memory phenotype suggesting they are descendents of an even smaller progenitor pool
• CD4 T cells are virtually absent in the spleen of 1 week old mice, giving further evidence that CD4 T cell population in adults results from expansion of a small progenitor pool
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• effector T cells exhibit defective LFA-1 and VLA-4 integrin adhesion under shear flow conditions compared with control cells
• however, rolling on low-density P- or E-selectins is normal
|
|
• effector T cells fail to arrest on inflamed lymph node vessels and fail to enter inflamed skin compared with control cells
• chemokine-stimulated effector T cells exhibit impaired motility inside inflamed lymph nodes compared with control cells
• however, effector T cells are recruited to skin-draining lymph nodes
|
|
• effector T cells exhibit defective LFA-1 and VLA-4 integrin adhesion under shear flow conditions compared with control cells
• however, rolling on low-density P- or E-selectins is normal
|
|
• effector T cells fail to arrest on inflamed lymph node vessels and fail to enter inflamed skin compared with control cells
• chemokine-stimulated effector T cells exhibit impaired motility inside inflamed lymph nodes compared with control cells
• however, effector T cells are recruited to skin-draining lymph nodes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired cytotoxic CD8+ T cell differentiation following viral infection
• following viral infection, differentiation is skewed exclusively toward the Type 17 fate
|
|
• defect in accumulation of CD8+ T cells following viral infection
|
|
• deficiency in memory-phenotype CD8+ T cells
|
|
• CD8+ T cells have a severe defect in cytotoxic gene expression in response to viral peptide stimulation even when cellularity is normalized
|
|
• increase in IL17 expression in CD8+ T cells in response to stimulation with viral derived peptides
|
|
• persistent high titers of lymphocyte choriomeningitis virus
• progressive weight loss, not seen in controls, begins about 1 week after infection and is accompanied by extensive organ pathology and excessive neutrophil response
• depletion of CD8+ T cells prevents viral induced wasting, neutrophilia, and organ pathology
|
|
• increase in IL17 expression in CD8+ T cells in response to stimulation with viral derived peptides
|
|
• impaired cytotoxic CD8+ T cell differentiation following viral infection
• following viral infection, differentiation is skewed exclusively toward the Type 17 fate
|
|
• defect in accumulation of CD8+ T cells following viral infection
|
|
• deficiency in memory-phenotype CD8+ T cells
|
|
• CD8+ T cells have a severe defect in cytotoxic gene expression in response to viral peptide stimulation even when cellularity is normalized
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells have increased mitochondrial mass relative to wild-type
|
|
• T cells are 10% larger than controls both before and after stimulation due to the accumulation of material from impairment in autophagy
• in the absence of growth factor stimulation (in vitro neglect assays) purified unstimulated T cells exhibit decreased survival due to impairment in autophagy
|
|
• defect in proliferation following either antibody-mediated TCR cross-linking or allogeneic stimulation
• In vivo CD4+ T cell proliferation is decreased to 42% as compared to 68% in wild-type
• In vivo CD8+ T cell proliferation is decreased to 51% as compared to 61% in wild-type
|
|
• T cells have increased ROS production relative to wild-type
|
|
• T cells are 10% larger than controls both before and after stimulation due to the accumulation of material from impairment in autophagy
• in the absence of growth factor stimulation (in vitro neglect assays) purified unstimulated T cells exhibit decreased survival due to impairment in autophagy
|
|
• T cells are 10% larger than controls both before and after stimulation
• T cells have increased mitochondrial mass relative to wild-type
|
|
• loss of CD8 T cells is more pronounced than loss of CD4 T cells, resulting in an elevated CD4:CD8 ratio
|
|
• absolute number of splenic T cells is reduced by 67% relative to controls
• B cell numbers are unchanged
|
|
• decreased survival of purified unstimulated T cells during in vitro neglect assays (cultured without stimulation)
|
|
• defect in proliferation following either antibody-mediated TCR cross-linking or allogeneic stimulation
• In vivo CD4+ T cell proliferation is decreased to 42% as compared to 68% in wild-type
• In vivo CD8+ T cell proliferation is decreased to 51% as compared to 61% in wild-type
|
|
• T cells are 10% larger than controls both before and after stimulation
• T cells have increased mitochondrial mass relative to wild-type
|
|
• loss of CD8 T cells is more pronounced than loss of CD4 T cells, resulting in an elevated CD4:CD8 ratio
|
|
• absolute number of splenic T cells is reduced by 67% relative to controls
• B cell numbers are unchanged
|
|
• decreased survival of purified unstimulated T cells during in vitro neglect assays (cultured without stimulation)
|
|
• defect in proliferation following either antibody-mediated TCR cross-linking or allogeneic stimulation
• In vivo CD4+ T cell proliferation is decreased to 42% as compared to 68% in wild-type
• In vivo CD8+ T cell proliferation is decreased to 51% as compared to 61% in wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells have increased mitochondrial mass relative to wild-type
|
|
• nutrient restricted purified naive T cells treated with cholorquine do not exhibit autophagic degradation activity (autophagic flux) in contrast to wild-type controls
• T cells are 10% larger than controls both before and after stimulation due to the accumulation of material from impairment in autophagy
• increased survival of purified unstimulated T cells during in vitro neglect assays (cultured without stimulation)
|
|
• defect in proliferation following either antibody-mediated TCR cross-linking or allogeneic stimulation
• In vivo CD4+ T cell proliferation is decreased to 53% as compared to 68% in wild-type
• In vivo CD8+ T cell proliferation is decreased to 51% as compared to 61% in wild-type
|
|
• T cells have increased ROS production relative to wild-type
|
|
• T cells are 10% larger than controls both before and after stimulation
• T cells have increased mitochondrial mass relative to wild-type
|
|
• loss of CD8 T cells is more pronounced than loss of CD4 T cells, resulting in an elevated CD4:CD8 ratio
|
|
• absolute number of splenic T cells is reduced by 32% relative to controls
• B cell numbers are unchanged
|
|
• increased survival of purified unstimulated T cells during in vitro neglect assays (cultured without stimulation) as compared to controls
|
|
• defect in proliferation following either antibody-mediated TCR cross-linking or allogeneic stimulation
• In vivo CD4+ T cell proliferation is decreased to 53% as compared to 68% in wild-type
• In vivo CD8+ T cell proliferation is decreased to 51% as compared to 61% in wild-type
|
|
• T cells are 10% larger than controls both before and after stimulation
• T cells have increased mitochondrial mass relative to wild-type
|
|
• loss of CD8 T cells is more pronounced than loss of CD4 T cells, resulting in an elevated CD4:CD8 ratio
|
|
• absolute number of splenic T cells is reduced by 32% relative to controls
• B cell numbers are unchanged
|
|
• increased survival of purified unstimulated T cells during in vitro neglect assays (cultured without stimulation) as compared to controls
|
|
• defect in proliferation following either antibody-mediated TCR cross-linking or allogeneic stimulation
• In vivo CD4+ T cell proliferation is decreased to 53% as compared to 68% in wild-type
• In vivo CD8+ T cell proliferation is decreased to 51% as compared to 61% in wild-type
|
|
• nutrient restricted purified naive T cells treated with cholorquine do not exhibit autophagic degradation activity (autophagic flux) in contrast to wild-type controls
• T cells are 10% larger than controls both before and after stimulation due to the accumulation of material from impairment in autophagy
• increased survival of purified unstimulated T cells during in vitro neglect assays (cultured without stimulation)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• unlike mice with T-cell specific conditional deletion of Eomes that also lack expression of Tbx21, clearance of lymphocyte choriomeningitis virus is similar to wild-type controls
|
|
• deficiency in memory-phenotype CD8+ T cells
|
|
• deficiency in memory-phenotype CD8+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• stimulation of cultured thymocytes with anti-CD3 or combination of anti-CD3 and anti-CD28 does not result in increased cell death of double positive T cells from mutant mice like treatment induces in thymocytes from wild-type mice
|
|
• there is a significant reduction in CD4+ and mature CD8+ thymocyte numbers in adult mutant mice but absolute cellularity doesn't differ between mutants and wild-type mice
• thymic cellularity in 5 week-old mice is reduced by around 50%; absolute cellularity of double positive, CD4+ and CD8+ cells is reduced significantly
|
|
• there is a dramatic reduction in percentage of CD4+ thymocytes to less than 1% of the thymic cell population compared to that of wild-type littermates
|
|
• relative percentage of CD8+ thymocytes is reduced by 40-60% of that in wild-type littermates
• most of the cells in the CD8+ compartment in mutants are immature compared to cells in the wild-type
|
|
• mutant mice have about 2-fold more gamma delta T cells compared to 5 week-old control littermates
|
|
• stimulation of cultured thymocytes with anti-CD3 or combination of anti-CD3 and anti-CD28 does not result in increased cell death of double positive T cells from mutant mice like treatment induces in thymocytes from wild-type mice
|
|
• there is a significant reduction in CD4+ and mature CD8+ thymocyte numbers in adult mutant mice but absolute cellularity doesn't differ between mutants and wild-type mice
• thymic cellularity in 5 week-old mice is reduced by around 50%; absolute cellularity of double positive, CD4+ and CD8+ cells is reduced significantly
|
|
• there is a dramatic reduction in percentage of CD4+ thymocytes to less than 1% of the thymic cell population compared to that of wild-type littermates
|
|
• relative percentage of CD8+ thymocytes is reduced by 40-60% of that in wild-type littermates
• most of the cells in the CD8+ compartment in mutants are immature compared to cells in the wild-type
|
|
• mutant mice have about 2-fold more gamma delta T cells compared to 5 week-old control littermates
|
|
• stimulation of cultured thymocytes with anti-CD3 or combination of anti-CD3 and anti-CD28 does not result in increased cell death of double positive T cells from mutant mice like treatment induces in thymocytes from wild-type mice
|
|
• there is a significant reduction in CD4+ and mature CD8+ thymocyte numbers in adult mutant mice but absolute cellularity doesn't differ between mutants and wild-type mice
• thymic cellularity in 5 week-old mice is reduced by around 50%; absolute cellularity of double positive, CD4+ and CD8+ cells is reduced significantly
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal adult hematopoiesis
|
| N |
• mice exhibit normal B cell and T cell development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mature T cell numbers in the spleen and lymph nodes are decreased compared to in Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
• however, the proportion of T cells with naive, memory and regulatory phenotypes are normal
|
|
• CD4+ T cells are less responsive to IL-7 and exhibit a reduced survival compared to CD4+ T cells from IL-7-treated Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
|
|
• increase in cellular size following stimulation, an indication of activation, is substantially reduced in T cells compared to in T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
|
|
• T cells stimulated with anti-CD3 and anti-CD28 or with phorbol 12-myristate 13-acetate (PMA) and ionomycin fail to proliferate as well as T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes even with the addition of IL-2
• cell cycling in T cells is reduced or absent compared to in T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
• however, no increase in T cell apoptosis is observed
|
|
• T cells stimulated with anti-CD3 and anti-CD28 or with phorbol 12-myristate 13-acetate (PMA) and ionomycin produce less IL-2 than similarly treated wild-type cells
|
|
• mature T cell numbers in the spleen and lymph nodes are decreased compared to in Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
• however, the proportion of T cells with naive, memory and regulatory phenotypes are normal
|
|
• CD4+ T cells are less responsive to IL-7 and exhibit a reduced survival compared to CD4+ T cells from IL-7-treated Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
|
|
• increase in cellular size following stimulation, an indication of activation, is substantially reduced in T cells compared to in T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
|
|
• T cells stimulated with anti-CD3 and anti-CD28 or with phorbol 12-myristate 13-acetate (PMA) and ionomycin fail to proliferate as well as T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes even with the addition of IL-2
• cell cycling in T cells is reduced or absent compared to in T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
• however, no increase in T cell apoptosis is observed
|
|
• T cells stimulated with anti-CD3 and anti-CD28 or with phorbol 12-myristate 13-acetate (PMA) and ionomycin fail to proliferate as well as T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes even with the addition of IL-2
• cell cycling in T cells is reduced or absent compared to in T cells from Cops8tm1Nwe Tg(CD4-cre)1Cwi heterozygotes
• however, no increase in T cell apoptosis is observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• of CD4+ T cells following TCR stimulation
|
|
• stimulated CD4+ T cell exhibit modestly reduced proliferation compared with control cells
|
|
• less than 2-fold in untreated mice
• in MOG treated mice
|
|
• more than 3-fold
|
|
• reduced survival and decreased proliferation of stimulated CD4+ T cells after 72 hours in culture
• CD4+ T cells cultured in TH0, TH1 and TH2 conditions exhibit increased susceptibility to cell death compared with control cells
• CD4+ T cells cultured in TH17 conditions exhibit decreased susceptibility to cell death compared with control cells
|
|
• mice treated with MOG exhibit complete resistance to experimental autoimmune encephalomyelitis with a very minor decrease in total CD4+ T cells in the spleens and lymph nodes, a great reduction in IFNG-gamma+ CD4+ T cells, modestly reduced IL17+ CD4+ T cells and absence of CD4+ T cells infiltration in the central nervous system compared with control mice
|
|
• of CD4+ T cells following TCR stimulation
|
|
• stimulated CD4+ T cell exhibit modestly reduced proliferation compared with control cells
|
|
• of CD4+ T cells following TCR stimulation
|
|
• stimulated CD4+ T cell exhibit modestly reduced proliferation compared with control cells
|
|
• less than 2-fold in untreated mice
• in MOG treated mice
|
|
• more than 3-fold
|
|
• reduced survival and decreased proliferation of stimulated CD4+ T cells after 72 hours in culture
• CD4+ T cells cultured in TH0, TH1 and TH2 conditions exhibit increased susceptibility to cell death compared with control cells
• CD4+ T cells cultured in TH17 conditions exhibit decreased susceptibility to cell death compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not develop any overt autoimmunity or inflammation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD4 T cells proliferate in vitro at normal levels when stimulated with anti-CD3 antibody compared
|
|
• increased number of CD44highCD62low T cells in the spleen and lymph nodes
|
|
• increased number of CD69+ T cells are found in the spleen and lymph nodes
|
|
• CD4 T cells secrete IL-2 upon stimulation with anti -CD3 or -CD3/-CD28 antibodies
|
|
• CD4 T cells proliferate in vitro at normal levels when stimulated with anti-CD3 antibody compared
|
|
• increased number of CD44highCD62low T cells in the spleen and lymph nodes
|
|
• increased number of CD69+ T cells are found in the spleen and lymph nodes
|
|
• CD4 T cells proliferate in vitro at normal levels when stimulated with anti-CD3 antibody compared
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• proliferation of anti-CD3 and APC stimulated CD4+ cells is decreased compared with wild-type cells
|
|
• mice exhibit an increase in the thymic CD4 to CD8 ratio compared to in wild-type mice (3:1 vs. 9:1)
|
|
• regardless of skewing conditions, T cells fail to differentiate into effector Th1 or Th2 cells unlike similarly treated wild-type mice
• transgene vaccinia-specified T cells fail to differentiate into Th1 effector cells unlike similarly treated wild-type mice
• under skewing conditions, T cells fail to differentiate into Th17 cells unlike similarly treated wild-type mice
|
|
• mice exhibit an increase in the thymic CD4 to CD8 ratio compared to in wild-type mice (3:1 vs. 9:1)
• however, CD4 to CD8 ratios in the spleen, peripheral blood, and lymph nodes are normal
|
|
• TCR engagement, following stimulation with anti-CD3 and APCs, IL2, or IL2 and IL7, leads to increased regulatory T cell differentiation compared to similarly treated wild-type cells
|
|
• anti-CD3 and anti-CD28 stimulated T cells produce less IFN-gamma compared with similarly treated wild-type cells
|
|
• following stimulation with PMA and ionomycin, only 1.1% of T cells isolated from the Peyer's patches produce IL17 compared to 3.8% of similarly treated wild-type cells
|
|
• transgene vaccinia-specified donor T cells subjected to ex vivo rechallenge exhibit increased IL2 production compared with similarly treated wild-type mice
|
|
• transgene vaccinia-specified donor T cells subjected to ex vivo rechallenge exhibit increased TNF-alpha production compared with similarly treated wild-type mice
|
|
• proliferation of anti-CD3 and APC stimulated CD4+ cells is decreased compared with wild-type cells
|
|
• mice exhibit an increase in the thymic CD4 to CD8 ratio compared to in wild-type mice (3:1 vs. 9:1)
|
|
• regardless of skewing conditions, T cells fail to differentiate into effector Th1 or Th2 cells unlike similarly treated wild-type mice
• transgene vaccinia-specified T cells fail to differentiate into Th1 effector cells unlike similarly treated wild-type mice
• under skewing conditions, T cells fail to differentiate into Th17 cells unlike similarly treated wild-type mice
|
|
• mice exhibit an increase in the thymic CD4 to CD8 ratio compared to in wild-type mice (3:1 vs. 9:1)
• however, CD4 to CD8 ratios in the spleen, peripheral blood, and lymph nodes are normal
|
|
• TCR engagement, following stimulation with anti-CD3 and APCs, IL2, or IL2 and IL7, leads to increased regulatory T cell differentiation compared to similarly treated wild-type cells
|
|
• mice exhibit an increase in the thymic CD4 to CD8 ratio compared to in wild-type mice (3:1 vs. 9:1)
|
|
• proliferation of anti-CD3 and APC stimulated CD4+ cells is decreased compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells prematurely acquire single positive phenotype compared to in wild-type mice
|
|
• mice present with CD+TCR- T cell population not found in controls
|
|
• T cells prematurely acquire single positive phenotype compared to in wild-type mice
|
|
• mice present with CD+TCR- T cell population not found in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• anti-Fas antibody fails to induce cell death in T-cells as it does in controls
• resistant to FasL induced cell death
|
| N |
• thymus, spleen, and lymph nodes all appear to be normal
|
|
• peripheral B-cells are increased in number
|
|
• TCR activation of T-cells is reduced
|
|
• both CD4+ and CD8+ peripheral T-cells are reduced in number
• peripheral T-cells divide less efficiently when transplanted to Rag1 deficient mice
|
|
• peripheral B-cells are increased in number
|
|
• TCR activation of T-cells is reduced
|
|
• both CD4+ and CD8+ peripheral T-cells are reduced in number
• peripheral T-cells divide less efficiently when transplanted to Rag1 deficient mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased
• accumulate in the CNS rather than the spleen in experimental autoimmune encephalitis
|
|
• earlier onset and aggravated disease course during the T-cell dependent phase
• difference from controls disappears after 15 days
• increased number of CD4+ T cells at the beginning of clinical disease (day 8) and at the disease peak (day 13) but not at day 18
• three fold increase in myelin oligodendrocyte glycoprotein specific T cells at disease peak
|
|
• increased
• accumulate in the CNS rather than the spleen in experimental autoimmune encephalitis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the thymus
|
|
• in the thymus
|
|
• in the thymus
|
|
• in the thymus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• in the absence of STING activation, mice show no significant differences in the frequencies of thymocytes, splenic T cells, and splenic myeloid cells relative to control mice
• splenocytes show normal frequencies of CD3+ (T cells), CD19+ (B cells) and CD3- (non-T non-B cells) relative to CD45+ cells; normal CD4+ and CD8+ T cells relative to total CD3+ cells; normal central memory and effector memory CD4+ and CD8+ T cells; and normal FoxP3+ CD4+ regulatory T cells (Tregs)
• moreover, splenocytes show normal frequencies of Ly6G+CD11b+ neutrophils relative to total CD3- splenocytes; normal Ly6Chi CD11b+ monocytes relative to total Ly6G- splenocytes; and normal F4/80midCD11b+ macrophages and F4/80hiCD11b- red pulp macrophages relative to total Ly6Clo splenocytes
• thymocytes show normal frequencies of double-negative (DN), double-positive (DP), and single-positive CD4 and CD8 T cells and normal frequencies of DN subsets
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• enhanced Th2 response in an allergic asthma model, more so than in Cishtm1.2Cdon homozygotes
|
|
• in the bronchoalveolar lavage fluid following induction of asthma
|
|
• enhanced asthmatic response with more total cells and eosinophils in the bronchoalveolar lavage fluid
|
|
• from Th2 cells in an allergic asthma model
|
|
• from lung-associated lymph node cells and splenocytes re-stimulated ex vivo with ovalbumin
|
|
• increased CD4+ IL4+ cells among lung infiltrates in a model of asthma
• from lung-associated lymph node cells and splenocytes re-stimulated ex vivo with ovalbumin
|
|
• from lung-associated lymph node cells and splenocytes re-stimulated ex vivo with ovalbumin
|
|
• enhanced Th2 response in an allergic asthma model, more so than in Cishtm1.2Cdon homozygotes
|
|
• in the bronchoalveolar lavage fluid following induction of asthma
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice treated with MOG(35-55) along with pertussis toxin exhibit normal EAE clinical scores
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• no defects in T cell development in the thymus, spleen, or lymph nodes are dectected
• no alteration in cell viability, expression of cell surface activation markers, cell cycle progression, or cell size
|
|
• moderate suppression of overall proliferation after activation in vitro
|
|
• enhanced anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
• inhibition in vitro
• however, there is no significant change in Th2 cell differentiation in vitro
|
|
• inhibition of differentiation in vitro
• treatment with NV118 (cell permeable succinate analogue) partially restores differentiation
|
|
• enhanced anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
• significant protection from EAE pathogenic progression with more infiltrated FoxP3+CD4+ T cells and fewer infiltrated inflammatory CD4+T cells
|
|
• moderate suppression of overall proliferation after activation in vitro
|
|
• moderate suppression of overall proliferation after activation in vitro
|
|
• enhanced anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
• inhibition in vitro
• however, there is no significant change in Th2 cell differentiation in vitro
|
|
• inhibition of differentiation in vitro
• treatment with NV118 (cell permeable succinate analogue) partially restores differentiation
|
|
• enhanced anti-inflammatory induced T regulatory cell differentiation in vitro
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• T follicular helper cell development is restored compared with Id3tm2.1Cmu homozygotes
|
|
• partially restored compared with Id3tm2.1Cmu homozygotes
|
|
• partially restored compared with Id3tm2.1Cmu homozygotes
|
|
• partially restored compared with Id3tm2.1Cmu homozygotes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal T cell viability and numbers and lymph node size
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cell numbers in the spleen and lymph nodes are reduced 80-90% compared to Rag-null OT-II controls
|
|
• T cell numbers in the spleen and lymph nodes are reduced 80-90% compared to Rag-null OT-II controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the Il7r transgene rescues the low T cell numbers observed in mice with Foxo1-deficient OT-II T cells
|
|
• the Il7r transgene rescues the low T cell numbers observed in mice with Foxo1-deficient OT-II T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• CD8+ numbers and CD8+/CD4+ ratio recovered from condition in mice lacking Tg(H2-K-BCL2)1Josd
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• elevated serum IL-17 concentration
|
|
• elevated serum IL-17 concentration
|
|
• increased amounts of IL-17 protein in the culture supernatants of CD4+ T cells activated with anti-CD3 and anti-CD28
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• elevated serum IL-17 concentration
|
|
• elevated serum IL-17 concentration
|
|
• increased amounts of IL-17 protein in the culture supernatants of CD4+ T cells activated with anti-CD3 and anti-CD28
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal regulatory T cell development in the thymus, maintenance in the periphery and suppression ability in vitro
|
|
• regulatory T cells exhibit reduced ability to drive Th17 differentiation compared with wild-type cells
|
|
• regulatory T cells exhibit reduced ability to drive Th17 differentiation compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number of mature T cells in the spleen is less than 10% of wild-type
|
|
• slight increase in the frequency
|
|
• the number of mature T cells in the spleen is less than 10% of wild-type
|
|
• the frequency of total CD4+ thymocytes and mature CD4+ thymocytes is decreased compared to in wild-type mice
• few CD4+ T cells are detected
|
|
• the frequency of CD8+ T cells is reduced by greater than 80% compared to in wild-type mice
• the frequency of mature CD8+ thymocytes is reduced over 10-fold compared to in wild-type mice
• few CD8+ T cells are detected
|
|
• the number of mature T cells in the spleen is less than 10% of wild-type
|
|
• slight increase in the frequency
|
|
• the number of mature T cells in the spleen is less than 10% of wild-type
|
|
• the frequency of total CD4+ thymocytes and mature CD4+ thymocytes is decreased compared to in wild-type mice
• few CD4+ T cells are detected
|
|
• the frequency of CD8+ T cells is reduced by greater than 80% compared to in wild-type mice
• the frequency of mature CD8+ thymocytes is reduced over 10-fold compared to in wild-type mice
• few CD8+ T cells are detected
|
|
• the number of mature T cells in the spleen is less than 10% of wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased B cell lineages
|
|
• slightly
• number of double negative thymocytes is doubled
|
|
• generation of mature CD4+ cells is impaired
• 2-3 fold reduction of proliferation in the thymus
|
|
• generation of mature CD4+ cells is impaired
• 2-3 fold reduction of proliferation in the thymus
|
|
• reduced frequency of stage 3 invariant NKT cells
• double negative invariant NKT cells are reduced
|
|
• increased in the thymus by 1.5 fold
|
|
• increased B cell lineages
|
|
• slightly
• number of double negative thymocytes is doubled
|
|
• generation of mature CD4+ cells is impaired
• 2-3 fold reduction of proliferation in the thymus
|
|
• generation of mature CD4+ cells is impaired
• 2-3 fold reduction of proliferation in the thymus
|
|
• reduced frequency of stage 3 invariant NKT cells
• double negative invariant NKT cells are reduced
|
|
• increased in the thymus by 1.5 fold
|
|
• slightly
• number of double negative thymocytes is doubled
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as determined by transplantation experiments, defects in Th17 cell differentiation occur in an autocrine manner
|
|
• as determined by transplantation experiments, defects in Th17 cell differentiation occur in an autocrine manner
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal percentages and total cell numbers of double positive or single positive thymocytes and CD4+ or CD8+ peripheral T cells in the spleen
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ and CD8+ T cells in the spleen
|
|
• with altered follicular structure and widely scattered T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
• slightly
|
|
• slightly
|
|
• slightly
|
|
• from un-stimulated splenic T cells
|
|
• from un-stimulated and stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• from stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• from un-stimulated splenic T cells
|
|
• systemic inflammation
|
|
• slightly
|
|
• slightly
|
|
• slightly
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ and CD8+ T cells in the spleen
|
|
• with altered follicular structure and widely scattered T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
• with expanded T cell pool, mainly CD4+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• colitis results when mutant bone marrow is used to reconstitute irradiated Rag null mice
• in these bone marrow chimeras, only 7% of CD4+ T cells are regulatory T cells compared to 30% in control chimeras
|
|
• there is a slight increase in the number of single-positive Tcr-betahi CD4+ and CD8+ mature thymocytes
|
|
• despite increased proliferation upon activation, T cells have decreased homeostatic proliferation with only a10-20% recovery rate of wild-type in competitive bone marrow chimera assays
|
|
• a higher percentage of CD4+T cells activated in vitro produce IFN-gamma, IL-4, IL-10 or IL-17 compared to controls
|
|
• a higher percentage of CD8+ T cells activated in vitro produce IFN-gamma compared to controls
|
|
• an increased percentage of splenic T cells exhibit an activated CD44hiCD62Llo or CD69+ phenotype
• there is about a 3-fold increase in activated CD4 T cells and a 5- to 10- fold increase in activated CD8 T cells
• a higher percentage of these activated T cells can produce IL-17 or IFN-gamma upon restimulation compared to activated wild-type T cells
|
|
• mice have lymphadenopathy resulting from a rapidly proliferating CD4+ T cell population
|
|
• mice have lymphadenopathy resulting from a rapidly proliferating CD4+ T cell population
|
|
• mice 5-6 months of age have elevated levels of anti-nuclear antigens
|
|
• mice 5-6 months of age have elevated levels of anti-dsDNA antigens
|
|
• colitis results when mutant bone marrow is used to reconstitute irradiated Rag null mice
• in these bone marrow chimeras, only 7% of CD4+ T cells are regulatory T cells compared to 30% in control chimeras
|
|
• there is a slight increase in the number of single-positive Tcr-betahi CD4+ and CD8+ mature thymocytes
|
|
• despite increased proliferation upon activation, T cells have decreased homeostatic proliferation with only a10-20% recovery rate of wild-type in competitive bone marrow chimera assays
|
|
• a higher percentage of CD4+T cells activated in vitro produce IFN-gamma, IL-4, IL-10 or IL-17 compared to controls
|
|
• a higher percentage of CD8+ T cells activated in vitro produce IFN-gamma compared to controls
|
|
• an increased percentage of splenic T cells exhibit an activated CD44hiCD62Llo or CD69+ phenotype
• there is about a 3-fold increase in activated CD4 T cells and a 5- to 10- fold increase in activated CD8 T cells
• a higher percentage of these activated T cells can produce IL-17 or IFN-gamma upon restimulation compared to activated wild-type T cells
|
|
• mice have lymphadenopathy resulting from a rapidly proliferating CD4+ T cell population
|
|
• mice have lymphadenopathy resulting from a rapidly proliferating CD4+ T cell population
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• Foxp3+ regulatory T cells are increased 2-fold relative to wild-type mice
• the numbers of regulatory T cells is increased in the peripheral and mesenteric lymph nodes, spleens and among the lamina propria mononuclear cell infiltrate of the colon
• proliferation of Foxp3+ cells and CD4+CD8+Foxp3- cells is increased in association with the development of colitis
|
|
|
• Foxp3+ regulatory T cells are increased 2-fold relative to wild-type mice
• the numbers of regulatory T cells is increased in the peripheral and mesenteric lymph nodes, spleens and among the lamina propria mononuclear cell infiltrate of the colon
• proliferation of Foxp3+ cells and CD4+CD8+Foxp3- cells is increased in association with the development of colitis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice begin to die at 6 months of age due to wasting and diarrhea
|
|
• T cells Th1, Th2 and CTL (cytotoxic T lymphocyte) differentiation is enhanced while Th17-cell differentiation is inhibited
• in the experimental autoimmune encephalomyelitis model, the number of IL-17 producing T cells is reduced in animals that do and those that do not develop encephalomyelitis
|
|
• as determined by transplantation experiments, defects in Th17 cell differentiation occur in an autocrine manner
|
|
• T cell activation is enhanced
|
|
• following activation, interferon-gamma levels are increased relative to in control cells
• in the experimental autoimmune encephalomyelitis model, only mice that develop encephalomyelitis produce great amounts of interferon-gamma
|
|
• following activation, IL-4 levels are increased whereas IL-17 levels are decreased relative to in control cells
|
|
• 6 of 8 mice did not develop encephalomyelitis and only 2 showed mild disease compared to controls which all develop severe disease
• the number of IL-17 producing T cells is reduced in animals that do and those that do not develop encephalomyelitis
• only mice that develop encephalomyelitis produce great amounts of interferon-gamma
|
|
• mice present with mononuclear infiltrate in the lungs, parenchyma of the liver, and colon
|
|
• severe colitis is associated with disruption of the crypt architecture, crypt abscess formation and epithelium hyperplasia
|
|
• epithelium hyperplasia is associated with colitis
|
|
• disruption of crypt architecture is associated with colitis
|
|
• associated with colitis
|
|
• at 4 to 12 months of age, heavy mononuclear cell infiltrate of the lamina propria and subglandular areas of the colon is detected
|
|
• severe colitis is associated with disruption of the crypt architecture, crypt abscess formation and epithelium hyperplasia
|
|
• mononuclear cell clusters are detected in the parenchyma of mice with colitis
|
|
• IgG deposits accumulate in the glomeruli
|
|
• mononuclear cell infiltrate is present in the lungs of mice with colitis
|
|
• disruption of crypt architecture is associated with colitis
|
|
• associated with colitis
|
|
• T cells Th1, Th2 and CTL (cytotoxic T lymphocyte) differentiation is enhanced while Th17-cell differentiation is inhibited
• in the experimental autoimmune encephalomyelitis model, the number of IL-17 producing T cells is reduced in animals that do and those that do not develop encephalomyelitis
|
|
• as determined by transplantation experiments, defects in Th17 cell differentiation occur in an autocrine manner
|
|
• T cell activation is enhanced
|
|
• following activation, interferon-gamma levels are increased relative to in control cells
• in the experimental autoimmune encephalomyelitis model, only mice that develop encephalomyelitis produce great amounts of interferon-gamma
|
|
• following activation, IL-4 levels are increased whereas IL-17 levels are decreased relative to in control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice die by three weeks of age from a rampant wasting autoimmune disease
|
|
• more T cells in these mice are in an activated state with CD69 and CD44 upregulated and CD62L downregulated
|
|
• mice suffer from a generalized autoimmune disease
|
|
• liver inflammation occurs in these mice before death
• portal tracts are enlarged, contain congested vessels, and are infiltrated by numerous lymphocytes
|
|
• liver inflammation occurs in these mice before death
• portal tracts are enlarged, contain congested vessels, and are infiltrated by numerous lymphocytes
|
|
• more T cells in these mice are in an activated state with CD69 and CD44 upregulated and CD62L downregulated
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice present with a similar inflammatory disorder as seen in B9d2/Tgfb1tm1Flv/ Tgfb1tm2Flv Tg(CD4-cre)1Cwi mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• tamoxifen-treated mice exhibit no gross functional defects in mature T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the frequency of double positive T cells is reduced to 45% of thymocytes compared to 85% in wild-type mice
• the absolute number of double positive cells is 10% of wild-type
|
|
• the frequency of double positive T cells is reduced to 45% of thymocytes compared to 85% in wild-type mice
• the absolute number of double positive cells is 10% of wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• CD4 T cell differentiation is normal
|
|
• stimulated CD4+ T cells are larger than similarly treated wild-type cells
|
|
• in ovalbumin challenged mice
|
|
• under Th1 conditions, splenocytes produce less IFN-gamma than similarly treated wild-type cells
|
|
• under Th2 conditions, splenocytes produce less IL4, IL5, and IL13 compared with similarly treated wild-type cells
|
|
• in splenocytes under Th1 conditions
|
|
• in splenocytes under Th2 conditions
|
|
• in splenocytes under Th2 conditions
|
|
• in splenocytes under Th2 conditions
|
|
• ovalbumin-treated mice exhibit no increase in eosinophils and lymphocytes in the bronchoalveolar lavage fluid, reduced infiltration of cells in the peribronchiolar and perivascular regions of the lung and decreased mucus production unlike wild-type mice
|
|
• following methacholine treatment, ovalbumin sensitized and challenged mice fail to exhibit an increase in airway resistance unlike similarly treated wild-type mice
|
|
• following methacholine treatment, ovalbumin sensitized and challenged mice fail to exhibit airway hyperresponsiveness unlike similarly treated wild-type mice
|
|
• Th2 cells exhibit a dramatic increase in DNA methylation in the il4 promoter and CNS-1 region unlike similarly treated wild-type cells that exhibit a decrease in DNA methylation in this region
|
|
• stimulated CD4+ T cells are larger than similarly treated wild-type cells
|
|
• in ovalbumin challenged mice
|
|
• under Th1 conditions, splenocytes produce less IFN-gamma than similarly treated wild-type cells
|
|
• under Th2 conditions, splenocytes produce less IL4, IL5, and IL13 compared with similarly treated wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• single positive (SP) alpha-beta thymocytes express high levels of CXCR3
• CD8+ SP thymocytes express higher levels of CXCR3 than CD4+ SP thymocytes
• mixed bone marrow chimera experiments suggest CXCR3 expression is extrinsic to the thymocytes
• SP thymocytes secrete high levels of IL-4
• mixed bone marrow chimera experiments also demonstrate that a cell intrinsic defect in emigration of mutant single positive thymocytes from the thymus
|
|
• mice have severe T cell lymphopenia
|
|
• single positive thymocytes are increased
|
|
• IgE levels are increased 33-fold
|
|
• IgG1 levels are modestly increased
|
|
• single positive (SP) alpha-beta thymocytes express high levels of CXCR3
• CD8+ SP thymocytes express higher levels of CXCR3 than CD4+ SP thymocytes
• mixed bone marrow chimera experiments suggest CXCR3 expression is extrinsic to the thymocytes
• SP thymocytes secrete high levels of IL-4
• mixed bone marrow chimera experiments also demonstrate that a cell intrinsic defect in emigration of mutant single positive thymocytes from the thymus
|
|
• mice have severe T cell lymphopenia
|
|
• single positive thymocytes are increased
|
|
• IgE levels are increased 33-fold
|
|
• IgG1 levels are modestly increased
|
|
• single-positive thymocytes produce about four-fold more IL-4 compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Th1 and Tc1 cells show a total lack of migration toward CXCL10
|
|
• CD44+ effector/memory T cells are reduced in both CD4+ and CD8+ T cells
|
|
• Th1 and Tc1 cells show a total lack of migration toward CXCL10
|
|
• CD44+ effector/memory T cells are reduced in both CD4+ and CD8+ T cells
|
|
• by CD8 cells cultured for 4 days under Th1 conditions
|
|
• when CD8+ T cells are cultured in Th17-polarizing conditions 3 fold more IL17 producing cells are produced
|
|
• when CD8+ T cells are cultured in Tc2-polarizing conditions 3 fold more IL4 producing cells are produced
|
|
• 60% of mice vaccinated against B16 melenoma still grow tumors upon B16 injection
|
|
• Th1 and Tc1 cells show a total lack of migration toward CXCL10
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the peripheral blood
|
|
• mice exhibit T cell lymphopenia
|
|
• CD4+ T cells are reduced in the spleens, lymph nodes, and peripheral blood mononuclear cells compared to in wild-type mice
• however, thymic CD4+ counts are normal
|
|
• CD8+ T cells are reduced in the spleens, lymph nodes, and peripheral blood mononuclear cells compared to in wild-type mice
• however, thymic CD8+ counts are normal
|
|
• in the peripheral blood
|
|
• mice exhibit T cell lymphopenia
|
|
• CD4+ T cells are reduced in the spleens, lymph nodes, and peripheral blood mononuclear cells compared to in wild-type mice
• however, thymic CD4+ counts are normal
|
|
• CD8+ T cells are reduced in the spleens, lymph nodes, and peripheral blood mononuclear cells compared to in wild-type mice
• however, thymic CD8+ counts are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• mice exhibit peripheral T cell lymphopenia
|
|
|
• mice exhibit peripheral T cell lymphopenia
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• regulatory T cells fail to drive Th17 differentiation
|
|
• regulatory T cells fail to drive Th17 differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• regulatory T cells fail to drive Th17 differentiation
|
|
• regulatory T cells fail to drive Th17 differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the thymus
|
|
• in the thymus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• almost complete absence of activated CD4+ and CD8+ T lymphocyte proliferation
|
|
• T lymphocyte counts are diminished
• however, cellularity and cell population distribution of blood, thymus, and spleen are normal
|
|
• almost complete absence of activated CD4+ and CD8+ T lymphocyte proliferation
|
|
• T lymphocyte counts are diminished
• however, cellularity and cell population distribution of blood, thymus, and spleen are normal
|
|
• almost complete absence of activated CD4+ and CD8+ T lymphocyte proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T lymphocytes show reduced proliferation
|
|
• T lymphocytes show reduced proliferation
|
|
• T lymphocytes show reduced proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• both CD4 and CD8 enriched splenic T cells show a reduction in proliferation upon CD3/CD28 stimulation
|
|
• after 3 days of activation, an increase of naive (CD44-CD62L+) T cells is seen
|
|
• after 3 days of activation, a reduction of effector memory cells (CD44+CD62L-) is seen
|
|
• both CD4 and CD8 enriched splenic T cells show a reduction in proliferation upon CD3/CD28 stimulation
|
|
• after 3 days of activation, an increase of naive (CD44-CD62L+) T cells is seen
|
|
• after 3 days of activation, a reduction of effector memory cells (CD44+CD62L-) is seen
|
|
• both CD4 and CD8 enriched splenic T cells show a reduction in proliferation upon CD3/CD28 stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• lose significantly more weight following dextran sulfate sodium treatment compared to controls
|
|
• increased number of colon tumors in mice treated with azoxymethane followed by 3 cycles of dextran sulfate sodium administration compared to controls
• tumors are predominantly distributed in the distal colon and 80% of mice show rectal prolapse
|
|
• isolated splenic CD4+ T cells develop significantly fewer T-helper 17 cells under polarizing conditions
|
|
• increased number of colon tumors in mice treated with azoxymethane followed by 3 cycles of dextran sulfate sodium administration compared to controls
• tumors are predominantly distributed in the distal colon and 80% of mice show rectal prolapse
|
|
• lose significantly more weight following dextran sulfate sodium treatment compared to controls
|
|
• isolated splenic CD4+ T cells develop significantly fewer T-helper 17 cells under polarizing conditions
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• peripheral T cells are less mature
• reduction of mature T cells in spleen and lymph nodes
|
|
• peripheral T cells are less mature
• reduction of mature T cells in spleen and lymph nodes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells expressing the transgenic MHC class II-restricted TCR show diversion from the CD4+ lineage to the CD8+ lineage
|
|
• T cells expressing the transgenic MHC class II-restricted TCR show diversion from the CD4+ lineage to the CD8+ lineage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decrease in IL4 secretion from CD4 T cells isolated from SRBC-immunized mice as compared to control
• increase in IL10 secretion (20 fold) from activated CD4 T cells as compared to control
• increase in apoptotic markers (caspase 3 and annexin V) in PD-1high follicular T helper cells from spleen at 10 days post-immunization
|
|
• analysis of spleens at 10 days post-immunization with sheep red blood cells (SRBC) reveals almost complete loss of Fas+ GL7+PNA+ germinal center B cells
|
|
• analysis of spleens at 10 days post-immunization with sheep red blood cells (SRBC) reveals almost complete loss of CXCR5+ ICOS+PD-1high follicular T helper cells
|
|
• SRBC specific IgG titers post-immunization are 5 fold lower than controls
|
|
• increase in IL10 secretion (20 fold) from activated CD4 T cells as compared to control
|
|
• decrease in IL4 secretion from CD4 T cells isolated from SRBC-immunized mice as compared to control
|
|
• decrease in IL4 secretion from CD4 T cells isolated from SRBC-immunized mice as compared to control
• increase in IL10 secretion (20 fold) from activated CD4 T cells as compared to control
• increase in apoptotic markers (caspase 3 and annexin V) in PD-1high follicular T helper cells from spleen at 10 days post-immunization
|
|
• analysis of spleens at 10 days post-immunization with sheep red blood cells (SRBC) reveals almost complete loss of Fas+ GL7+PNA+ germinal center B cells
|
|
• analysis of spleens at 10 days post-immunization with sheep red blood cells (SRBC) reveals almost complete loss of CXCR5+ ICOS+PD-1high follicular T helper cells
|
|
• SRBC specific IgG titers post-immunization are 5 fold lower than controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a significant reduction in percentage of positively-selected thymocytes but there is still a substantial population of single positive thymocytes
|
|
• there is a significant reduction in percentage of positively-selected thymocytes but there is still a substantial population of single positive thymocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• positive selection is diminished significantly
|
|
• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 24 compared to 257 in non transgenic littermates
|
|
• positive selection is diminished significantly
|
|
• CD4 to CD8 ratio (% of mature CD4 and CD8 T cells) is 24 compared to 257 in non transgenic littermates
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in male mice, which undergo negative selection, compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• in male mice, which undergo negative selection, compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• in male mice, which undergo negative selection, compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• female mice, which undergo positive selection, exhibit a decrease in total CD8 single positive cells and CD8 single positive cells in the T3-70hi cell compartment compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• male mice, which undergo negative selection, exhibit an increase in CD8 single positive cells in the T3-70hi cell compartment compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• in male mice, which undergo negative selection, compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• in male mice, which undergo negative selection, compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• in male mice, which undergo negative selection, compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• female mice, which undergo positive selection, exhibit a decrease in total CD8 single positive cells and CD8 single positive cells in the T3-70hi cell compartment compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• male mice, which undergo negative selection, exhibit an increase in CD8 single positive cells in the T3-70hi cell compartment compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
• in male mice, which undergo negative selection, compared with Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Tg(TcraH-Y,TcrbH-Y)71Vbo mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following reactivation
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• peripheral T cells are reduced compared to in wild-type mice
• in transplantation experiments, T cells are less competitive than wild-type T cells
|
|
• in the thymus
|
|
• in the thymus
|
|
• CD4+ thymocytes are more profoundly decreased than CD8+ thymocytes
|
|
• mice exhibit an increase in T cell activation compared with wild-type mice
• however, activation phenotype is not cell intrinsic
|
|
• in response to stimulation with anti-CD3m anti-CD3/anti-CD28, or anti-CD3/IL2, T cell proliferation is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
• however, treatment with PMA/ionomycin restores proliferation
|
|
• YFP+ T regulatory cells exhibit reduced ability to suppress naive T cell proliferation compared with wild-type T cells
|
|
• following anti-CD3/anti-CD28 stimulation, slightly fewer IFN-gamma producing single positive T cells are detected compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
|
|
• following anti-CD3/anti-CD28 stimulation, IL2 production by single positive T cells is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
|
|
• mice exhibit dermatitis unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• mice weight less than wild-type mice
• however, transfer of regulatory T cells restores normal weight gain
|
|
• mice exhibit rectal prolapse unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• following reactivation
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• differentiation into CD4 or CD8 single positive thymocytes is reduced compared to in wild-type mice
|
|
• peripheral T cells are reduced compared to in wild-type mice
• in transplantation experiments, T cells are less competitive than wild-type T cells
|
|
• in the thymus
|
|
• in the thymus
|
|
• CD4+ thymocytes are more profoundly decreased than CD8+ thymocytes
|
|
• mice exhibit an increase in T cell activation compared with wild-type mice
• however, activation phenotype is not cell intrinsic
|
|
• in response to stimulation with anti-CD3m anti-CD3/anti-CD28, or anti-CD3/IL2, T cell proliferation is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
• however, treatment with PMA/ionomycin restores proliferation
|
|
• YFP+ T regulatory cells exhibit reduced ability to suppress naive T cell proliferation compared with wild-type T cells
|
|
• mice exhibit dermatitis unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• mice exhibit alopecia unlike wild-type mice
• however, treatment with wild-type T regulatory cells prevents development of symptom
|
|
• following reactivation
|
|
• in response to stimulation with anti-CD3m anti-CD3/anti-CD28, or anti-CD3/IL2, T cell proliferation is reduced compared to in similarly treated Plcg1tm1Gcrp/Plcg1+ Tg(CD4-cre)1Cwi Gt(ROSA)26Sortm1(EYFP)Cos mice
• however, treatment with PMA/ionomycin restores proliferation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• severe reduction in single positive (SP) CD4 cells and no enrichment of SP CD8 cells
|
|
• severe reduction in single positive (SP) CD4 cells and no enrichment of SP CD8 cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice immunized with NP-CG exhibit normal development of memory B cells
|
|
• in mice immunized with NP-CG
|
|
• in mice immunized with NP-CG
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• gamma-irradiated thymus do not exhibit clonal growth of thymocytes or changes in thymocyte numbers or differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show no significant differences in the distribution of B cells, macrophages, monocytes, dendritic cells, and granulocytes relative to wild-type controls
|
|
• mice exhibit enhanced alpha4 integrin-mediated T cell migration and homing to the gut
|
|
• in a T cell-transfer model of chronic colitis, Rag1 null mice reconstituted with naive T cells (CD4+CD45RBhighCD25low) exhibit higher colitis clinical scores, increased infiltration of mononuclear cells in colonic lamina propria, more severe destruction of the epithelial barrier, and significantly more alpha4+ CD4+ T cells in the colon than control mice receiving wild-type naive T cells
• however, in vitro, naive T cells show normal proliferation and activation capacities relative to wild-type naive T cells
|
|
• flow cytometry analysis of T cell distribution showed significantly more T cells in the small intestine, colon, and Peyers patches than in wild-type controls
• however, T cell distribution in the bone marrow, thymus, spleen, and peripheral and mesenteric lymph nodes is normal
|
|
• CD4+ T cells show increased talin binding to alpha4 integrins and enhanced binding to soluble VCAM-1 and MAdCAM-1 (mucosal addressin cell adhesion molecule-1)
• however, splenic CD4+ T cells show normal expression levels of alpha4 integrin
|
|
• mice exhibit enhanced alpha4 integrin-mediated T cell migration and homing to the gut
|
|
• flow cytometry analysis of T cell distribution showed significantly more T cells in the small intestine, colon, and Peyers patches than in wild-type controls
• however, T cell distribution in the bone marrow, thymus, spleen, and peripheral and mesenteric lymph nodes is normal
|
|
• CD4+ T cells show increased talin binding to alpha4 integrins and enhanced binding to soluble VCAM-1 and MAdCAM-1 (mucosal addressin cell adhesion molecule-1)
• however, splenic CD4+ T cells show normal expression levels of alpha4 integrin
|
|
• mice exhibit enhanced alpha4 integrin-mediated T cell migration and homing to the gut
|
|
• in a single-cell random migration assay, CD4+ T cells show enhanced migration on immobilized VCAM-1 and MAdCAM-1 (mucosal addressin cell adhesion molecule-1) substrates, with a higher average velocity than wild-type T cells
|
|
• in a T cell-transfer model of chronic colitis, Rag1 null mice reconstituted with naive T cells (CD4+CD45RBhighCD25low) exhibit higher colitis clinical scores, increased infiltration of mononuclear cells in colonic lamina propria, more severe destruction of the epithelial barrier, and significantly more alpha4+ CD4+ T cells in the colon than control mice receiving wild-type naive T cells
• however, in vitro, naive T cells show normal proliferation and activation capacities relative to wild-type naive T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the number of B cells is normal
|
|
• in TCR-stimulated T cells
|
|
• in TCR-stimulated T cells
|
|
• impaired maturation of CD8 single positive thymocytes
|
|
• in the lymph node, spleen and peripheral blood
• 7.4-fold in the spleen
|
|
• 6.6-fold in the spleen
|
|
• impaired response to IL7
|
|
• in TCR-stimulated T cells
|
|
• in TCR-stimulated T cells
|
|
• in TCR-stimulated T cells
|
|
• in TCR-stimulated T cells
|
|
• in TCR-stimulated T cells
|
|
• impaired maturation of CD8 single positive thymocytes
|
|
• in the lymph node, spleen and peripheral blood
• 7.4-fold in the spleen
|
|
• 6.6-fold in the spleen
|
|
• impaired response to IL7
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in memory B cells from mice immunized with NP-CG
|
|
• in mice immunized with NP-CG at day 40 but not day 7
|
|
• NP-CG immunized mice fail to generate NP-specific germinal center B cells at day 40
|
|
• in mice immunized with NP-CG fail to develop T follicular helper cells at day 7 and 40
|
|
• memory B cells from mice treated with NP-CG produce low affinity antibodies in an IgG1 secondary response unlike wild-type cells
|
|
• in memory B cells from mice immunized with NP-CG
|
|
• in mice immunized with NP-CG at day 40 but not day 7
|
|
• NP-CG immunized mice fail to generate NP-specific germinal center B cells at day 40
|
|
• in mice immunized with NP-CG fail to develop T follicular helper cells at day 7 and 40
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• peripheral blood red blood cell numbers are mildly reduced
|
|
• hematocrit levels are mildly reduced
|
|
• hemoglobin levels are mildly reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mainly due to loss of cells with naive (CD44lo) phenotype
|
|
• in spleen and lymph node
|
|
• in spleen and lymph node
|
|
• T cells treated with BafA1 exhibit reduced autophagy activity compared with control cells
|
|
• mainly due to loss of cells with naive (CD44lo) phenotype
|
|
• in spleen and lymph node
|
|
• in spleen and lymph node
|
|
• T cells treated with BafA1 exhibit reduced autophagy activity compared with control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• constitutively active Map2k1(MEK) rescues thymocyte development restoring single positive thymocyte and splenic T cell populations
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• contrary to germ line deletion, mice are born in Mendelian ratios with no sex bias
|
| N |
• mice exhibit normal frequencies and numbers of B and T cells and activated T cells
• unchallenged mice exhibit no heightened inflammatory response and normal T regulator cell suppressor function
|
|
• flu-infected mice exhibit a greater decrease in average blood oxygen saturation, overall lung tissue damage and decreased surface temperature compared with wild-type mice
• however, flu-infected mice exhibit normal T cell activation and T regulatory cell mediated suppression of anti-viral immunity
|
|
• flu-infected mice exhibit a greater decrease in average blood oxygen saturation compared with wild-type mice
• however, mice do not exhibit anemia
|
|
• in flu-infected mice
• however, core body temperature is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• differentiation and maturation of CD4 single-positive (SP) and CD8 SP populations within the thymus are normal, with no significant alterations in the numbers of total, double-negative (DN), double-positive (DP), CD4 SP, and CD8 SP thymocytes
|
|
• after in vitro stimulation with anti-CD3epsilon and anti-CD28 mAbs, increase in CD4 SP thymocytes cell number is significantly lower than in control mice at days 3 and 5 post-stimulation
• after stimulation with anti-CD3epsilon and anti-CD28 mAbs for 4 h, CD4 SP thymocytes show higher mRNA expression of cell-cycle regulator Cdkn1a (p21Cip1) than control cells
• proliferation defect is not rescued in the presence of exogenous IL-2
|
|
• after in vitro stimulation with anti-CD3epsilon and anti-CD28 mAbs, CD4 SP thymocytes show significantly lower mRNA expression of genes involved in effector cell induction (Il2 and Tbx2)
|
|
• increased ratio of memory-phenotype versus naive T cells of either CD4 or CD8 cells in periphery
• many peripheral memory-phenotype T cells retain non-deleted floxed allele suggesting that Znf131-deficient naive T cells released from the thymus are unable to expand to maintain T cell homeostasis in periphery
|
|
• despite normal thymic selection and T cell maturation in the thymus, mice show a significant reduction in absolute numbers of CD3+, CD4+ and CD8+ cells in spleen
• naive T cells released from the thymus are not able to proliferate to maintain naive T cell pool in periphery
|
|
• significant reduction in absolute numbers of CD4+ cells in spleen
|
|
• significant reduction in absolute numbers of CD8+ cells in spleen
|
|
• after in vitro stimulation with anti-CD3epsilon and anti-CD28 mAbs, increase in CD4 SP thymocytes cell number is significantly lower than in control mice at days 3 and 5 post-stimulation
• after stimulation with anti-CD3epsilon and anti-CD28 mAbs for 4 h, CD4 SP thymocytes show higher mRNA expression of cell-cycle regulator Cdkn1a (p21Cip1) than control cells
• proliferation defect is not rescued in the presence of exogenous IL-2
|
|
• after in vitro stimulation with anti-CD3epsilon and anti-CD28 mAbs, CD4 SP thymocytes show significantly lower mRNA expression of genes involved in effector cell induction (Il2 and Tbx2)
|
|
• increased ratio of memory-phenotype versus naive T cells of either CD4 or CD8 cells in periphery
• many peripheral memory-phenotype T cells retain non-deleted floxed allele suggesting that Znf131-deficient naive T cells released from the thymus are unable to expand to maintain T cell homeostasis in periphery
|
|
• despite normal thymic selection and T cell maturation in the thymus, mice show a significant reduction in absolute numbers of CD3+, CD4+ and CD8+ cells in spleen
• naive T cells released from the thymus are not able to proliferate to maintain naive T cell pool in periphery
|
|
• significant reduction in absolute numbers of CD4+ cells in spleen
|
|
• significant reduction in absolute numbers of CD8+ cells in spleen
|
|
• after in vitro stimulation with anti-CD3epsilon and anti-CD28 mAbs, CD4 SP thymocytes show significantly lower mRNA expression of genes involved in effector cell induction (Il2 and Tbx2)
|
|
• after in vitro stimulation with anti-CD3epsilon and anti-CD28 mAbs, increase in CD4 SP thymocytes cell number is significantly lower than in control mice at days 3 and 5 post-stimulation
• after stimulation with anti-CD3epsilon and anti-CD28 mAbs for 4 h, CD4 SP thymocytes show higher mRNA expression of cell-cycle regulator Cdkn1a (p21Cip1) than control cells
• proliferation defect is not rescued in the presence of exogenous IL-2
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in vitro, naive splenic CD4+ T cells convert more efficiently into induced Foxp3-expressing regulatory T cells (Foxp3+ iTreg) in the presence of anti-CD3epsilon + TGFbeta
|
|
• in vitro stimulation of splenic CD4+ T cells with plate-bound anti-CD3epsilon in the presence of TGFbeta results in a significantly higher % of CD25+Foxp3+ cells within viable CD4+ T cells, consistent with enhanced conversion into Foxp3+ iTreg cells
|
|
• ex vivo splenocytes incubated with increasing concentrations of rhIL-2 show a small but significant decrease in the % of pSTAT5+ cells in conventional CD4+ T cells and CD8alpha+ T cells along with a marginal increase in the % of pSTAT5+ cells in CD4+Foxp3+ Treg cells
• however, ex vivo-sorted Foxp3+ Treg cells mixed with CFSE-labeled wild-type CD4+ T effector cells in the presence of nti-CD3epsilon/anti-CD28 show a normal capacity to inhibit CD4+ T-cell proliferation, and in vitro-induced Foxp3+ CD4 T cells show unchanged expression of suppressive molecules, indicating normal Treg suppressive function
|
|
• in vitro stimulation of splenic CD4+ T cells with plate-bound anti-CD3epsilon in the presence of TGFbeta results in significantly increased IL-2 production after 48 h of culture
|
|
• in vitro, naive splenic CD4+ T cells convert more efficiently into induced Foxp3-expressing regulatory T cells (Foxp3+ iTreg) in the presence of anti-CD3epsilon + TGFbeta
|
|
• in vitro stimulation of splenic CD4+ T cells with plate-bound anti-CD3epsilon in the presence of TGFbeta results in a significantly higher % of CD25+Foxp3+ cells within viable CD4+ T cells, consistent with enhanced conversion into Foxp3+ iTreg cells
|
|
• ex vivo splenocytes incubated with increasing concentrations of rhIL-2 show a small but significant decrease in the % of pSTAT5+ cells in conventional CD4+ T cells and CD8alpha+ T cells along with a marginal increase in the % of pSTAT5+ cells in CD4+Foxp3+ Treg cells
• however, ex vivo-sorted Foxp3+ Treg cells mixed with CFSE-labeled wild-type CD4+ T effector cells in the presence of nti-CD3epsilon/anti-CD28 show a normal capacity to inhibit CD4+ T-cell proliferation, and in vitro-induced Foxp3+ CD4 T cells show unchanged expression of suppressive molecules, indicating normal Treg suppressive function
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the thymus, spleen and liver of mice treated with alpha- galactosylceramide CD1d1 tetramer
|
|
• in the thymus, spleen and liver of mice treated with alpha- galactosylceramide CD1d1 tetramer
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit about 50% survival at 8-10 months of age
|
|
• mice develop T-cell lymphoblastic leukemia, with dense neoplastic infiltrates in the cranial mediastinum characterized by medium to large-sized atypical lymphoid cells with numerous mitotic figures and dissemination to the heart
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| T-cell adult acute lymphocytic leukemia | DOID:5602 | J:263520 | ||
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a minor but significant increase in the number of granulocytes in the blood
|
|
• despite high levels of IL-17A expression by T cells, there is no difference in onset or severity of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide (MOG) compared to controls
|
|
• increased numbers of neutrophils are recruited into the spleen compared to controls after immunization with MOG peptide
|
|
• immunization with MOG peptide plus adjuvant leads a highly significant increase in serum IL-17A levels
|
|
• T cells constitutively express high levels of IL-17A
• this secretion is greatly enhanced after T cell stimulation
|
|
• immunization with MOG peptide plus adjuvant leads a highly significant increase in serum IL-17A levels
|
|
• there is a minor but significant increase in the number of granulocytes in the blood
|
|
• increased numbers of neutrophils are recruited into the spleen compared to controls after immunization with MOG peptide
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• spleen and lymph nodes are nearly devoid of T cells
|
|
• only a mild reduction in the CD4 single-positive cells in the thymus
|
|
• 50% reduction in CD8 single-positive cells in the thymus
|
|
• loss of single positive thymocytes during final maturation stages in the thymus
|
|
• spleen and lymph nodes are nearly devoid of T cells
|
|
• only a mild reduction in the CD4 single-positive cells in the thymus
|
|
• 50% reduction in CD8 single-positive cells in the thymus
|
|
• loss of single positive thymocytes during final maturation stages in the thymus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• loss of peripheral CD8+ T cells
|
|
• loss of peripheral CD8+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced IL17-expressing splenic gamma-delta T cells
|
|
• reduced IL17-expressing splenic gamma-delta T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• abnormal NK T cell maturation
|
|
• 23 times more in the thymus
• 43 times more in the spleen
• in mice treated with galactosylceramide
|
|
• abnormal NK T cell maturation
|
|
• 23 times more in the thymus
• 43 times more in the spleen
• in mice treated with galactosylceramide
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal numbers of IL17-producing thymic gamma-delta T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit a largely normal distribution of lymphocyte populations
|
|
• of re-stimulated T cells from MOG 35-55 treated mice
• of T cells stimulated with concanavalin
|
|
• decreased
|
|
• small decrease of CD4+ and CD8+ activated T cells in the peripheral lymphoid organs
|
|
• in splenocytes from MOG 35-55-treated mice
|
|
• during Th17 differentiation
|
|
• mice treated with MOG 35-55 exhibit reduced incidence and severity (reduced inflammation, demyelination and axonal damage) of experimental autoimmune encephalomyelitis despite slightly earlier onset of paralysis compared with control mice
|
|
• in T-cells stimulated with anti-CD3/CD28 and IL2 compared with similarly treated T cells from Tg(CD2-Smad7) mice
|
|
• of re-stimulated T cells from MOG 35-55 treated mice
• of T cells stimulated with concanavalin
|
|
• decreased
|
|
• small decrease of CD4+ and CD8+ activated T cells in the peripheral lymphoid organs
|
|
• of re-stimulated T cells from MOG 35-55 treated mice
• of T cells stimulated with concanavalin
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significant decrease in IgG2a levels in response to TNP-OVA immunization as compared to control
|
|
• significant decrease in IgG2b levels in response to TNP-OVA immunization as compared to control
|
|
• significant decrease in IgG2a levels in response to TNP-OVA immunization as compared to control
|
|
• significant decrease in IgG2b levels in response to TNP-OVA immunization as compared to control
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following stimulation with anti-CD3 and anti-CD28 antibodies
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• eosinophilic inflammation
|
|
• in the esophagus, small bowel and lung and to a lesser extent in the skin
|
|
• in the spleen
|
|
• later with lesser eosinophil infiltration than in Ndfip1Gt(RRD002)Byg homozygotes
|
|
• eosinophilic inflammation
|
|
• later with lesser eosinophil infiltration than in Ndfip1Gt(RRD002)Byg homozygotes
|
|
• in the esophagus, small bowel and lung and to a lesser extent in the skin
|
|
• in the spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• however, treatment with anti-IL17A antibodies improves survival
|
|
• modest increase in IFNG+ T cells (that also express IL17) indicating a slight expansion of Th1 cells
|
|
• in the gut and lungs
|
|
• in the peripheral lymph nodes and lungs
|
|
• by peripheral T cells
|
|
• Th17 cells infiltrate the airways and cause severe neutrophilic lung inflammation with thickening of the airway epithelium, hypertrophy of the smooth muscle surrounding large and midsized airways and pronounced perivascular, increased mucus production and peribronchial/peribronchiolar inflammatory infiltrates
• however, lung phenotype is improved by treatment with anti-IL17A antibodies
|
|
• Th17 cells infiltrate the airways and cause severe neutrophilic lung inflammation with thickening of the airway epithelium, hypertrophy of the smooth muscle surrounding large and midsized airways and pronounced perivascular, increased mucus production and peribronchial/peribronchiolar inflammatory infiltrates
• however, lung phenotype is improved by treatment with anti-IL17A antibodies
|
|
• modest increase in IFNG+ T cells (that also express IL17) indicating a slight expansion of Th1 cells
|
|
• in the gut and lungs
|
|
• in the peripheral lymph nodes and lungs
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells are defective in homeostatic proliferation in a lymphopenic host compared with similarly treated wild-type cells
|
|
• T cell egression from the thymus is impaired compared to in wild-type mice
|
|
• the number of conventional alpha/beta T cells are reduced in the liver, spleen, lymph nodes, and blood compared with wild-type mice
|
|
• NK1.1-/CD44- stage 1 cells are decreased 4-fold compared to in wild-type mice
• NK1.1-/CD44- stage 2 and 3 cells are decreased greater than 4-fold compared to in wild-type mice
|
|
• invariant NK T cells are absent from the liver unlike in wild-type mice
• however, mice exhibit normal frequencies of conventional NK cells in the liver
|
|
• CD8+ cells exhibit reduced surface expression of CD8 compared to in wild-type mice
• TCRbetahigh CD8+ single positive thymocytes exhibit a 2-fold reduction in CD8 expression compared with wild-type cells
|
|
• invariant NK T cell development is blocked as cells transit stage 1
|
| N |
• thymocyte numbers and the subpopulations are normal
|
|
• T cells are defective in homeostatic proliferation in a lymphopenic host compared with similarly treated wild-type cells
|
|
• T cell egression from the thymus is impaired compared to in wild-type mice
|
|
• the number of conventional alpha/beta T cells are reduced in the liver, spleen, lymph nodes, and blood compared with wild-type mice
|
|
• NK1.1-/CD44- stage 1 cells are decreased 4-fold compared to in wild-type mice
• NK1.1-/CD44- stage 2 and 3 cells are decreased greater than 4-fold compared to in wild-type mice
|
|
• invariant NK T cells are absent from the liver unlike in wild-type mice
• however, mice exhibit normal frequencies of conventional NK cells in the liver
|
|
• CD8+ cells exhibit reduced surface expression of CD8 compared to in wild-type mice
• TCRbetahigh CD8+ single positive thymocytes exhibit a 2-fold reduction in CD8 expression compared with wild-type cells
|
|
• invariant NK T cell development is blocked as cells transit stage 1
|
|
• T cells are defective in homeostatic proliferation in a lymphopenic host compared with similarly treated wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD4+ T cells are impaired in their ability to proliferate and secrete IFN-gamma and IL-17 in response to immunization with ovalbumin (OVA) in the presence of lipopolysaccharide (LPS) followed by restimulation with OVA in the presence of irradiated splenocytes as antigen presenting cells
• CD4+ T cell response is defective in response to immunization with OVA plus either polyIC or CpG DNA
• mice depleted of CD25+ Treg cells (with a monoclonal anti-CD25 antibody) prior to immunization with OVA and LPS or OVA and CpG DNA are unable to restore the Th17 cell response, however the Th1 cell response is restored, with restoration of proliferation and secretion of IFN-gamma by restimulated CD4+ T cells
• however, clonal expansion of antigen-specific CD4+ T cells is not impaired
|
|
• upon immunization with 2W peptide in the presence of LPS, the Th1 response is impaired, with the number of cells in the draining lymph nodes reduced compared to that of controls, leading to a reduction in the absolute number of CD4+ T cells specific for the 2W peptide
|
|
• mice show absence of a Th17 cell response in response to immunization and restimulation
• however, mice do not exhibit an increased frequency of FoxP3+ Treg cells in unimmunized or immunized state, indicating normal numbers of iTreg cells
|
|
• memory T cells are generated at similar frequencies to wild-type following immunization with OVA and LPS, however, CD4+ memory T cells are impaired in their ability to differentiate into IFN-gamma secreting T cells after secondary immunization, even under conditions where Treg cells are absent during both the primary and secondary immunization
|
|
• CD4+ T cells are impaired in their ability to proliferate and secrete IFN-gamma and IL-17 in response to immunization with ovalbumin (OVA) in the presence of lipopolysaccharide (LPS) followed by restimulation with OVA in the presence of irradiated splenocytes as antigen presenting cells
• CD4+ T cell response is defective in response to immunization with OVA plus either polyIC or CpG DNA
• mice depleted of CD25+ Treg cells (with a monoclonal anti-CD25 antibody) prior to immunization with OVA and LPS or OVA and CpG DNA are unable to restore the Th17 cell response, however the Th1 cell response is restored, with restoration of proliferation and secretion of IFN-gamma by restimulated CD4+ T cells
• however, clonal expansion of antigen-specific CD4+ T cells is not impaired
|
|
• upon immunization with 2W peptide in the presence of LPS, the Th1 response is impaired, with the number of cells in the draining lymph nodes reduced compared to that of controls, leading to a reduction in the absolute number of CD4+ T cells specific for the 2W peptide
|
|
• mice show absence of a Th17 cell response in response to immunization and restimulation
• however, mice do not exhibit an increased frequency of FoxP3+ Treg cells in unimmunized or immunized state, indicating normal numbers of iTreg cells
|
|
• memory T cells are generated at similar frequencies to wild-type following immunization with OVA and LPS, however, CD4+ memory T cells are impaired in their ability to differentiate into IFN-gamma secreting T cells after secondary immunization, even under conditions where Treg cells are absent during both the primary and secondary immunization
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• synthesis of C16:0 and C18:1 fatty acids by Listeria infected T cells is reduced relative to controls
• total quantities of C16:0, C18:0, and C18:1 are not significantly changed 24 hours after activation with Listeria
|
| N |
• thymocyte T cell profiles are normal
• peripheral B cell numbers are normal
|
|
• CD8+ T cells in spleen and peripheral lymph nodes are dramatically reduced
• significant reductions in CD4+ T cells are also observed
|
|
• reduced activated memory T cell numbers
|
|
• reduced survival of peripheral CD8+ T cells
• supplementation of cultured cells with exogenous fatty acids improves survival
|
|
• CD8+ T cells in spleen and peripheral lymph nodes are dramatically reduced
• significant reductions in CD4+ T cells are also observed
|
|
• reduced activated memory T cell numbers
|
|
• reduced survival of peripheral CD8+ T cells
• supplementation of cultured cells with exogenous fatty acids improves survival
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• significant CD8+ T cell expansion after Listeria-OVA exposure
• cell survival is reduced
|
|
• significant CD8+ T cell expansion after Listeria-OVA exposure
• cell survival is reduced
|
|
• significant CD8+ T cell expansion after Listeria-OVA exposure
• cell survival is reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• regulatory T cells fail to respond to TCR stimulation or IL2 unlike wild-type cells
• however, regulatory T cells respond normally to anti-CD3 and IL2 and are as suppressive as wild-type regulatory T cells
|
|
• regulatory T cells fail to respond to TCR stimulation or IL2 unlike wild-type cells
• however, regulatory T cells respond normally to anti-CD3 and IL2 and are as suppressive as wild-type regulatory T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• most of the reduction of CD4 T cells is due to missing regulatory and memory T cell subsets
|
|
• numbers of CD4+CD44+ and to a lesser extent CD8+CD44+, memory-type T cells are reduced
|
|
• numbers of CD4+CD25+ T cells (suppressor/regulatory T cells) are reduced
|
|
• most of the reduction of CD4 T cells is due to missing regulatory and memory T cell subsets
|
|
• numbers of CD4+CD44+ and to a lesser extent CD8+CD44+, memory-type T cells are reduced
|
|
• numbers of CD4+CD25+ T cells (suppressor/regulatory T cells) are reduced
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in anti-CD3 antibody-injected mice
|
| N |
• regulatory T cells exhibit normal suppressive function and function in a T cell transfer model of colitis
• mice do not exhibit any signs of autoimmunity
|
|
• anti-CD3 antibody-injected mice exhibit more severe inflammation in the lamina propria of the small intestine and with increased epithelial cell proliferation and death compared with control mice
|
|
• 2- to 3-fold reduction in single positive thymocytes
• however, the number of naive and memory CD4+ T cells are normal
|
|
• CD4+ T cells stimulated with PMA and ionomycin exhibit more Th17 cell differentiation compared with control cells
• increased IL17+ CD4+ T cells among intraepithelial lymphocytes
• increased Th17 cells in the small intestine, spleen and lymph node following injection of anti-CD3 antibodies
• however, Th2 cell differentiation is normal
|
|
• in the periphery but not the thymus
|
|
• following injection of anti-CD3 antibodies
|
|
• increased IL17A in CD8+ T cell from naive mice and regulatory T cells after TCR stimulation
• increased IL17F in Th17 cells derived with TGFbeta and IL6 that persists after secondary and tertiary TCR stimulation
|
|
• in Th17 cells derived with TGFbeta and IL6
|
|
• in Th17 cells derived with TGFbeta and IL6
|
|
• following injection of anti-CD3 antibodies
|
|
• in anti-CD3 antibody-injected mice
|
|
• anti-CD3 antibody-injected mice exhibit more severe inflammation in the lamina propria of the small intestine and with increased epithelial cell proliferation and death compared with control mice
|
|
• 2- to 3-fold reduction in single positive thymocytes
• however, the number of naive and memory CD4+ T cells are normal
|
|
• 2- to 3-fold reduction in single positive thymocytes
• however, the number of naive and memory CD4+ T cells are normal
|
|
• CD4+ T cells stimulated with PMA and ionomycin exhibit more Th17 cell differentiation compared with control cells
• increased IL17+ CD4+ T cells among intraepithelial lymphocytes
• increased Th17 cells in the small intestine, spleen and lymph node following injection of anti-CD3 antibodies
• however, Th2 cell differentiation is normal
|
|
• in the periphery but not the thymus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal T cell development when exon 2 deletion occurs at the double + stage of T cell development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased cell numbers in mediastinal lymph nodes after TNP-OVA immunization
|
|
• increased number of lymphocytes, neutrophils, macrophages and eosinophils in BAL fluid and lung tissue after TNP-OVA immunization
• increased TNP-OVA-specific IgE and IgG1 levels in BAL and serum after OVA challenge
|
|
• increased cell numbers in lungs and bronchoalveolar lavage (BAL) fluid after TNP-OVA immunization
|
|
• increased cell numbers in lungs and bronchoalveolar lavage (BAL) fluid after TNP-OVA immunization
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following immunization with sheep red blood cells, mice exhibit a wild-type response in elevation of germinal center B cells and T follicular helper cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• following immunization with sheep red blood cells, mice exhibit a wild-type response in elevation of germinal center B cells and T follicular helper cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in young unimmunized mice with a further increase in mice immunized with sheep red blood cells
|
|
• in young unimmunized mice with a further increase in mice immunized with sheep red blood cells
|
|
• in mice immunized with sheep red blood cells
|
|
• in young unimmunized mice with a further increase in mice immunized with sheep red blood cells
|
|
• in young unimmunized mice with a further increase in mice immunized with sheep red blood cells
|
|
• in mice immunized with sheep red blood cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased lymphocyte infiltration in small intestine, lungs, liver, salivary glands and kidneys at age 6-7 months
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced differentiation to T-helper 2 and 17 cells in vitro
|
|
• reduced differentiation to effector T cells as determined by lower Tnfa, Ifng and Il2 production
|
|
• reduced number of Foxp+ CD4+ T cells in spleen
• normal number of Foxp+ CD4+ T cells in thymus and mesenteric lymph nodes
|
|
• reduced TH17 differentiation of naive CD4 T cells in vitro
|
|
• reduced TH2 differentiation of naive CD4 T cells in vitro
|
|
• reduced proliferative response after 36 h stimulation with anti-TCRbeta mAb plus anti-CD28 mAb in vitro
• reduced expansion of OVA-specific CD8+ T cells in spleen after OVA-peptide-expressing Listeria monocytogenes (Lm-OVA) infection
|
|
• reduced effector T cell differentiation of CD8+ T cells
|
|
• reduced number of invariant NKT cells in spleen
• normal number of invariant NKT cells in thymus and mesenteric lymph nod
|
|
• reduced Il2 production in CD4+ T cells
|
|
• no disease development, no body weight reduction, no CD3e+ T cell infiltration of spinal cord, reduced level of infiltrating cells, reduced demyelination in spinal cord after EAE induction
|
|
• significant decrease in mononuclear cells infiltrating lung peribronchiolar regions after intranasal administration of OVA following immunization with OVA
• less mucus production and goblet cell neoplasia in bronchioles after intranasal administration of OVA following immunization with OVA
|
| N |
• normal thymic T cell development and spleen T cell number
|
|
• reduced differentiation to T-helper 2 and 17 cells in vitro
|
|
• reduced differentiation to effector T cells as determined by lower Tnfa, Ifng and Il2 production
|
|
• reduced number of Foxp+ CD4+ T cells in spleen
• normal number of Foxp+ CD4+ T cells in thymus and mesenteric lymph nodes
|
|
• reduced TH17 differentiation of naive CD4 T cells in vitro
|
|
• reduced TH2 differentiation of naive CD4 T cells in vitro
|
|
• reduced proliferative response after 36 h stimulation with anti-TCRbeta mAb plus anti-CD28 mAb in vitro
• reduced expansion of OVA-specific CD8+ T cells in spleen after OVA-peptide-expressing Listeria monocytogenes (Lm-OVA) infection
|
|
• reduced effector T cell differentiation of CD8+ T cells
|
|
• reduced number of invariant NKT cells in spleen
• normal number of invariant NKT cells in thymus and mesenteric lymph nod
|
|
• lower basal oxygen consumption rate (OCR) and spare respiratory capacity (SRC) 24 h after TCR-stimulation in activated CD8+ T cells
• lower spare respiratory capacity (SRC) 24 h after TCR-stimulation in activated CD4+ T cells
• lower spare respiratory capacity (SRC) 8 h after TCR-stimulation in activated CD8+ T ce
• normal basal oxygen consumption rate (OCR) 24 h after TCR-stimulation in activated CD4+ T cells
• normal basal oxygen consumption rate (OCR) 8 h after TCR-stimulation in activated CD8+ T cells
|
|
• lower extracellular acidification rate (ECAR) 24 h after TCR- stimulation in activated CD4+ and activated CD8+ T cells
• normal extracellular acidification rate (ECAR) 8 h after TCR- stimulation in activated CD8+ T cells
|
|
• reduced intracellular tyrosine phosphorylation and ATP, lactate, NAD+ and NADH levels 24 h after TCR-stimulation in activated CD8+ T cells
• normal intracellular tyrosine phosphorylation and ATP, lactate, NAD+ and NADH levels 6 h after TCR-stimulation in activated CD8+ T cells
|
|
• reduced intracellular IMP, AMP, GMP and UMP levels 24 h after TCR-stimulation in activated CD8+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• despite inhibition of TORC1 activity, T cells exhibit normal regulatory T cell differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• activation of CD8+ T cells results in a more robust development of T effector cells
|
|
• CD4+ and CD8+ T cells in the spleen and lymph nodes exhibit an altered immune phenotype, characterized by elevated CD44high/CD62Llow, KLRG1high/CD127low subsets and increased expression of CD69 activation marker
|
|
• the frequency of CD4+ T cells in the lymph nodes and spleen is reduced
• mice have decreased absolute numbers of CD4+ T cells in secondary lymphoid organs
|
|
• CD8+ T cells have a molecular signature of T effector cells in response to activation with anti-CD3 and anti-CD28 mAbs
• CD8+T cells show a large accumulation of glycogen accompanied by an increase in UDP-glucose, the direct substrate for glycogen synthesis
• activated CD8+ T cells have higher mitochondria number per cell than activated control cells and exhibit altered mitochondria morphology with wider cristae and less tightly organized intermembrane space, a pattern seen in effector T cells
|
|
• the frequency of CD8+ T cells in the lymph nodes and spleen is reduced
• mice have decreased absolute numbers of CD8+ T cells in secondary lymphoid organs
|
|
• CD8+ T cells exhibit enhanced glucose uptake capacity
• CD8+ T cells exhibit elevated mitochondrial membrane potential and enhanced mitochondrial respiration
• CD8+ T cells show higher reactive oxygen species (ROS) content and mitochondrial ROS production after stimulation than control cells
• examination of mitochondrial fission proteins indicates that mitochondria fission machinery is hyperactivated in in stimulated CD8+ T cells
• CD8+ T cells show an elevated level of lipid peroxidation after stimulation
|
|
• activation of CD8+ T cells results in a more robust development of T effector cells
|
|
• CD4+ and CD8+ T cells in the spleen and lymph nodes exhibit an altered immune phenotype, characterized by elevated CD44high/CD62Llow, KLRG1high/CD127low subsets and increased expression of CD69 activation marker
|
|
• the frequency of CD4+ T cells in the lymph nodes and spleen is reduced
• mice have decreased absolute numbers of CD4+ T cells in secondary lymphoid organs
|
|
• CD8+ T cells have a molecular signature of T effector cells in response to activation with anti-CD3 and anti-CD28 mAbs
• CD8+T cells show a large accumulation of glycogen accompanied by an increase in UDP-glucose, the direct substrate for glycogen synthesis
• activated CD8+ T cells have higher mitochondria number per cell than activated control cells and exhibit altered mitochondria morphology with wider cristae and less tightly organized intermembrane space, a pattern seen in effector T cells
|
|
• the frequency of CD8+ T cells in the lymph nodes and spleen is reduced
• mice have decreased absolute numbers of CD8+ T cells in secondary lymphoid organs
|
|
• CD8+ T cells exhibit enhanced glucose uptake capacity
• CD8+ T cells exhibit elevated mitochondrial membrane potential and enhanced mitochondrial respiration
• CD8+ T cells show higher reactive oxygen species (ROS) content and mitochondrial ROS production after stimulation than control cells
• examination of mitochondrial fission proteins indicates that mitochondria fission machinery is hyperactivated in in stimulated CD8+ T cells
• CD8+ T cells show an elevated level of lipid peroxidation after stimulation
|
|
• CD8+T cells show a large accumulation of glycogen accompanied by an increase in UDP-glucose, the direct substrate for glycogen synthesis
• naive CD8+ T cells stimulated with anti-CD3 and anti-CD28 mAbs and IL-2 show glycogen buildup
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8+ T cells isolated from mutant mice show higher cytotoxic function when co-cultured with EG7 tumor cells in vitro
• congenic (CD45.1+) mice implanted with EG7 tumor cells followed by adoptive transfer of CD8+ T cells from mutant mice show smaller tumors that recipients of control T cells, indicating that antigen-specific T cells have more potent anti-tumor effector function
• recipients of mutant T cells are able to clear a Listeria monocytogenes-Ova infection more effectively than control mice
|
|
• CD8+ T cells isolated from mutant mice show higher cytotoxic function when co-cultured with EG7 tumor cells in vitro
• congenic (CD45.1+) mice implanted with EG7 tumor cells followed by adoptive transfer of CD8+ T cells from mutant mice show smaller tumors that recipients of control T cells, indicating that antigen-specific T cells have more potent anti-tumor effector function
• recipients of mutant T cells are able to clear a Listeria monocytogenes-Ova infection more effectively than control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8+ T cells co-cultured with B16-F10 melanoma cells uptake glucose more effectively than control cells
• adaptive transfer of mutant CD8+ T cells to congenic recipients bearing the B16-F10 melanoma results in smaller tumor growth than in controls
|
|
• CD8+ T cells co-cultured with B16-F10 melanoma cells uptake glucose more effectively than control cells
• adaptive transfer of mutant CD8+ T cells to congenic recipients bearing the B16-F10 melanoma results in smaller tumor growth than in controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hyperresponsive to stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• hyperresponsive to stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hyperresponsive to stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• increased production of IFNG following low level stimulation
|
|
• hyperresponsive to stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• based on marker expression, thymocyte positive selection is impaired and single positive thymocyte development is blocked unlike in wild-type mice
|
|
• the percentage of double positive thymocytes is slightly increased compared to in wild-type mice
• however, the absolute numbers of double positive thymocytes are normal
|
|
• the percentage of gamma delta T cells is increased compared to in wild-type mice
|
|
• few, if any
|
|
• the number of mature T cells is decreased compared to in wild-type mice
• few mature T cells are GFP+
|
|
• the number of CD4+ T cells is decreased 10-fold compared to in wild-type mice
• the CD4+ T cells that remain are GFP-
|
|
• the number of CD8+ T cells is decreased 20-fold compared to in wild-type mice
• the CD8+ T cells that remain are GFP-
• however, the number of immature single positive cells is normal
|
|
• TCR-mediated calcium fluxes are abrogated unlike in wild-type mice
|
|
• based on marker expression, thymocyte positive selection is impaired and single positive thymocyte development is blocked unlike in wild-type mice
|
|
• the percentage of double positive thymocytes is slightly increased compared to in wild-type mice
• however, the absolute numbers of double positive thymocytes are normal
|
|
• the percentage of gamma delta T cells is increased compared to in wild-type mice
|
|
• few, if any
|
|
• the number of mature T cells is decreased compared to in wild-type mice
• few mature T cells are GFP+
|
|
• the number of CD4+ T cells is decreased 10-fold compared to in wild-type mice
• the CD4+ T cells that remain are GFP-
|
|
• the number of CD8+ T cells is decreased 20-fold compared to in wild-type mice
• the CD8+ T cells that remain are GFP-
• however, the number of immature single positive cells is normal
|
|
• TCR-mediated calcium fluxes are abrogated unlike in wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• the number of NK T cells is decreased 30% to 50% compared to in wild-type mice
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• the number of NK T cells is decreased 30% to 50% compared to in wild-type mice
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
• following immunization with TNP-CGG
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD4 T cells from mice immunized with OVA antigen secrete almost 10-fold more IL-2 upon in vitro antigen restimulate compared to mice transgenic only for the T cell receptor
|
|
• OVA antigen specific T cells continue to proliferate upon antigen restimulation in a transfer model of tolerance
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased number of CD44highCD62low T cells are found in the spleen and lymph nodes
|
|
• increased number of CD69+ T cells are found in the spleen and lymph nodes
|
|
• CD4 T cells are resistant to anergy induced in vitro as measured by cellular proliferation in response to anti-CD3 restimulation
• proliferation rates are 5-10 fold higher upon restimulation compared to wild-type controls
• CD4 T cells expressing the Vbeta8 chain continue to proliferate upon restimulation with the superantigen SEB compared to CD4 T cells from control mice that are tolerized and do not proliferate in response to restimulation
|
|
• increased number of CD44highCD62low T cells are found in the spleen and lymph nodes
|
|
• increased number of CD69+ T cells are found in the spleen and lymph nodes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following 3 days of diptheria toxin injection, splenic T to B lymphocyte ratio is reduced from a mean of 0.5 in controls to 0.1 in double mutant animals
|
|
• numbers of CD4+ and CD8+ T lymphocytes are ~equally decreased
|
|
• following 3 days of diptheria toxin injection, splenic T to B lymphocyte ratio is reduced from a mean of 0.5 in controls to 0.1 in double mutant animals
|
|
• numbers of CD4+ and CD8+ T lymphocytes are ~equally decreased
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• APC/OVA primed peripheral CD8+ cells have significantly enhanced cytolitic efficiency
|
|
• under nonpolarizing conditions, IFNgamma levels are higher
|
|
• following infection with Alu/NP-CGG, B cell germinal centers are reduced 3-fold
|
|
• following infection with Alu/NP-CGG, Th2 cytokine levels are reduced
|
|
• following infection with Alu/NP-CGG, lower levels of IL-4, IL-5, and IL-13 are produced
• under nonpolarizing conditions, markedly lower levels of IL-4, IL-5, and IL-13 are produced
|
|
• following infection with S. mansoni, mice have smaller granulomas and somewhat reduced levels of eosinophils in the lung and significantly reduced levels of IL-13 Ralpha2 in serum
• in vitro exposure of lymph nodes with ConA or Schistosome egg antigen results in a reduced production of IL4 and IL5 and reduced proliferation of T cells
|
|
• under nonpolarizing conditions, IFNgamma levels are higher
|
|
• APC/OVA primed peripheral CD8+ cells have significantly enhanced cytolitic efficiency
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice show a moderate local response similar to controls after 3 injections of LPS into the flank
• 5 days after flank injection of CpG, mice develop moderate belt-shaped lesions similar to controls with no sign of necrosis or granulocyte infiltration,
|
|
• 9/10 mice survive 48 hour after LPS injection, whereas all completely IL-10-deficient mice die
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• there is a significant reduction in percentage of positively-selected thymocytes
|
|
• increase in double positive thymocytes and compensatory decrease in single positive numbers restores thymic cellularity compare to Mapk1/Lck-cre transgenics
|
|
• number of CD4 single positive thymocytes is decreased compared to wild-type
|
|
• number of CD8 single positive thymocytes is decreased compared to wild-type
|
|
• there is a significant reduction in percentage of positively-selected thymocytes
|
|
• increase in double positive thymocytes and compensatory decrease in single positive numbers restores thymic cellularity compare to Mapk1/Lck-cre transgenics
|
|
• number of CD4 single positive thymocytes is decreased compared to wild-type
|
|
• number of CD8 single positive thymocytes is decreased compared to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• hemizygous males exhibited increased lymph node cellularity at 14 days of age compared to controls
|
|
|
• hemizygous males developed lymphoproliferative autoimmune syndrome
|
|
|
• hemizygous males exhibited severe exfoliative dermatitis
|
|
|
• hemizygous males exhibited severe exfoliative dermatitis
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymocytes do not mature to the single positive stage
|
|
• percentage of single positive CD4 thymocytes is reduced from 10-15% in controls to 3% or less in mutants
|
|
• thymocytes do not mature to the single positive stage
|
|
• percentage of single positive CD4 thymocytes is reduced from 10-15% in controls to 3% or less in mutants
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD4+ T cells are reduced by about 20% in the periphery
|
|
• CD8+ T cells are reduced by about 50% in the periphery
|
|
• the antibody response to the T-dependent antigen NP-CG is delayed
|
|
• slight reduction in serum concentration of IgE following immunization with the T-dependent antigen NP-CG
|
|
• CD4+ T cells are reduced by about 20% in the periphery
|
|
• CD8+ T cells are reduced by about 50% in the periphery
|
|
• slight reduction in serum concentration of IgE following immunization with the T-dependent antigen NP-CG
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• increase in the numbers of apoptotic CD8+/HASlow/- and CD4+/HASlow/- mature thymocytes
|
|
|
• spleen and lymph nodes are nearly devoid of T cells
|
|
|
• only a mild reduction in the CD4 single-positive cells in the thymus
|
|
|
• 50% reduction in CD8 single-positive cells in the thymus
|
|
|
• loss of single-positive thymocytes during final maturation stages in the thymus
|
|
|
• increase in the numbers of apoptotic CD8+/HASlow/- and CD4+/HASlow/- mature thymocytes
|
|
|
• spleen and lymph nodes are nearly devoid of T cells
|
|
|
• only a mild reduction in the CD4 single-positive cells in the thymus
|
|
|
• 50% reduction in CD8 single-positive cells in the thymus
|
|
|
• loss of single-positive thymocytes during final maturation stages in the thymus
|
|
|
• increase in the numbers of apoptotic CD8+/HASlow/- and CD4+/HASlow/- mature thymocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• TCR-dependent T cell differentiation exhibit reduced potential to become Th1, Th17, and in vitro-induced Treg cells compared with wild-type cells
|
|
• decreased in the spleen
|
|
• increased in the lymph nodes
|
|
• decreased in the spleen
|
|
• increased in the lymph nodes
|
|
• in peripheral lymphatic organs
|
|
• after treatment with anti-CD3and anti-CD28 antibodies
• however, apoptosis rates remain wild-type
|
|
• TCR-dependent T cell differentiation exhibit reduced potential to become Th1, Th17, and in vitro-induced Treg cells compared with wild-type cells
|
|
• decreased in the spleen
|
|
• increased in the lymph nodes
|
|
• decreased in the spleen
|
|
• increased in the lymph nodes
|
|
• in peripheral lymphatic organs
|
|
• after treatment with anti-CD3and anti-CD28 antibodies
• however, apoptosis rates remain wild-type
|
|
• after treatment with anti-CD3and anti-CD28 antibodies
• however, apoptosis rates remain wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• after treatment with anti-CD3and anti-CD28 antibodies
|
|
• decreased in the spleen
|
|
• after treatment with anti-CD3and anti-CD28 antibodies
|
|
• decreased in the spleen
|
|
• after treatment with anti-CD3and anti-CD28 antibodies
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 4 of 5 mice had 2 fold enlargement
|
|
• 12-fold enlargement in the lymph nodes
• weight of the enlarged lymph nodes is still 200- to 300-fold less than in Fastm1.1Cgn Faslpr trans-heterozygous mice
|
|
• 4 of 5 mice had 2 fold enlargement
|
|
• 4 of 5 mice had 2 fold enlargement
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal T cell development
• unlike in Rc3h1san homozygotes, mice do not exhibit increased follicular T cell differentiation or germinal center formation
• mice exhibit normal autoimmunity
|
|
• doubled
|
|
• with a short-lived effector-like phenotype
|
|
• the number of monocytic macrophages is doubled compared to in control mice
|
|
• doubled
|
|
• with a short-lived effector-like phenotype
|
|
• the number of monocytic macrophages is doubled compared to in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD4+ T cells produce much less IL-2 and interferon-gamma after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
• however, calcium flux within CD4+ T cells are relatively normal
|
|
• T helper type 1 and 2 cells produce less IL-2, IL-4 and interferon-gamma compared to wild-type cells
|
|
• T helper type 1 and 2 cells produce less IL-2, IL-4 and interferon-gamma compared to wild-type cells
|
|
• CD4+ T cells produce much less interferon-gamma after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
• T helper type 1 and 2 cells produce less IL-2, IL-4 and interferon-gamma compared to wild-type cells
|
|
• CD4+ T cells produce much less IL-2 after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
• T helper type 1 and 2 cells produce less IL-2, IL-4 and interferon-gamma compared to wild-type cells
|
|
• T helper type 1 and 2 cells produce less IL-2, IL-4 and interferon-gamma compared to wild-type cells
|
|
• CD4+ T cells produce much less IL-2 and interferon-gamma after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
• however, calcium flux within CD4+ T cells are relatively normal
|
|
• T helper type 1 and 2 cells produce less IL-2, IL-4 and interferon-gamma compared to wild-type cells
|
|
• T helper type 1 and 2 cells produce less IL-2, IL-4 and interferon-gamma compared to wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit a milder lymphoproliferation than observed in Stim1tm1Rao/ Stim1tm1Rao Stim2tm1Rao/Stim2tm1Rao Tg(CD4-cre)1Cwi mice
|
|
• CD4+ T cells exhibit no calcium influx after depletion with thapsigargin or stimulation with anti-CD3 antibodies and ionomycin unlike wild-type cells
• CD4+ T cells fail to produce IL-2 after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies unlike wild-type cells
|
|
• CD4+ T cells fail to produce IL-2 after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies unlike wild-type cells
|
|
• mice exhibit a milder lymphoproliferation than observed in Stim1tm1Rao/ Stim1tm1Rao Stim2tm1Rao/Stim2tm1Rao Tg(CD4-cre)1Cwi mice
|
|
• CD4+ T cells exhibit no calcium influx after depletion with thapsigargin or stimulation with anti-CD3 antibodies and ionomycin unlike wild-type cells
• CD4+ T cells fail to produce IL-2 after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies unlike wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• Th1 and Tc1 cells show a small decrease in migration to CXCL10
|
|
• CD44+ effector/memory T cells are reduced in both CD4+ and CD8+ T cells
|
|
• Th1 and Tc1 cells show a small decrease in migration to CXCL10
|
|
• CD44+ effector/memory T cells are reduced in both CD4+ and CD8+ T cells
|
|
• 30% of mice allowed B16 melenoma tumor growth despite the vaccination against it
|
|
• Th1 and Tc1 cells show a small decrease in migration to CXCL10
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice produce more IgE+ B cells than wild-type mice
|
|
• mice produce more memory or effector T cells than wild-type mice
• as determined by bone marrow transplant assays, mice exhibit a cell-intrinsic defect in regulatory T cell development
|
|
• mice produce more CD11b+ IL-5R+ eosinophils or basophils than wild-type mice
|
|
• at 5 to 6 weeks of age, mice exhibit fewer regulatory T cells in the thymus, spleen and lymph nodes compared to wild-type mice due to a cell-intrinsic defect in regulatory T cell development
• while the proportion of regulatory T cells increases with age it remains 10% to 20% of wild-type
|
|
• in mice older than 8 weeks
|
|
• in mice older than 8 weeks
|
|
• T cells undergo reduced proliferation compared to wild-type cells after TCR stimulation
|
|
• CD4+ T cells exhibit no calcium influx after depletion with thapsigargin or stimulation with anti-CD3 antibodies and ionomycin unlike wild-type cells
• CD4+ T cells produce almost no IL-2 and very little interferon-gamma after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
|
|
• CD4+ T cells produce very little interferon-gamma after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
|
|
• CD4+ T cells produce almost no IL-2 after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
|
|
• in mice older than 8 weeks
|
|
• in mice older than 8 weeks
|
|
• in mice older than 8 weeks
|
|
• T cells undergo reduced proliferation compared to wild-type cells after TCR stimulation
|
|
• in mice older than 8 weeks
|
|
• mice produce more IgE+ B cells than wild-type mice
|
|
• mice produce more memory or effector T cells than wild-type mice
• as determined by bone marrow transplant assays, mice exhibit a cell-intrinsic defect in regulatory T cell development
|
|
• mice produce more CD11b+ IL-5R+ eosinophils or basophils than wild-type mice
|
|
• at 5 to 6 weeks of age, mice exhibit fewer regulatory T cells in the thymus, spleen and lymph nodes compared to wild-type mice due to a cell-intrinsic defect in regulatory T cell development
• while the proportion of regulatory T cells increases with age it remains 10% to 20% of wild-type
|
|
• CD4+ T cells exhibit no calcium influx after depletion with thapsigargin or stimulation with anti-CD3 antibodies and ionomycin unlike wild-type cells
• CD4+ T cells produce almost no IL-2 and very little interferon-gamma after stimulation with phorbol ester PMA and ionomycin or with anti-CD3 and anti-CD28 antibodies compared to wild-type cells
|
|
• in mice older than 8 weeks
|
|
• T cells undergo reduced proliferation compared to wild-type cells after TCR stimulation
|
|
• in mice older than 8 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells in a hypertonic solution exhibit reduced viability with a greater accumulation in G1 and G2/M phase, reduced DNA replication, and decreased expression of osmoprotective genes compared with similarly treated wild-type cells
• however, cell viability and cell cycle profile in isotonic conditions is normal
|
|
• T cells in a hypertonic solution exhibit reduced viability with a greater accumulation in G1 and G2/M phase, reduced DNA replication, and decreased expression of osmoprotective genes compared with similarly treated wild-type cells
• however, cell viability and cell cycle profile in isotonic conditions is normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal size of thymus, spleen and lymph nodes
• normal number of CD4 CD8 double-positive and double-negative thymocytes
• normal number of TCRB-lo CD69-lo and TCRB-int CD69-int thymocytes
|
|
• increased apoptosis of CD4+ CD8+ CD69+ thymocytes
|
|
• increased number of CD4+ CD8+ CD69+ and CD4+ CD8+ CD69- thymocytes in S and G2/M phase of cell cycle
|
|
• reduced number of TCRB-hi CD69-hi and TCRB-hi CD69-lo thymocytes
• reduced number of CD4+ CD69-hi and CD8+ CD69-hi thymocytes
• reduced number of CD24-lo TCRB-hi CD4+ and CD24-lo TCRB-hi CD8+ thymocytes
|
|
• reduced number in thymus, spleen and lymph nodes
• normal total number of thymocytes
|
|
• reduced number in thymus, spleen and lymph nodes
• normal total number of thymocytes
|
|
• increased number of CD44-hi CD62L-lo and CD44-hi CD62L-hi T cells in spleen and lymph nodes
|
|
• increased apoptosis of CD4+ CD8+ CD69+ thymocytes
|
|
• increased number of CD4+ CD8+ CD69+ and CD4+ CD8+ CD69- thymocytes in S and G2/M phase of cell cycle
|
|
• reduced number of TCRB-hi CD69-hi and TCRB-hi CD69-lo thymocytes
• reduced number of CD4+ CD69-hi and CD8+ CD69-hi thymocytes
• reduced number of CD24-lo TCRB-hi CD4+ and CD24-lo TCRB-hi CD8+ thymocytes
|
|
• reduced number in thymus, spleen and lymph nodes
• normal total number of thymocytes
|
|
• reduced number in thymus, spleen and lymph nodes
• normal total number of thymocytes
|
|
• increased number of CD44-hi CD62L-lo and CD44-hi CD62L-hi T cells in spleen and lymph nodes
|
|
• increased apoptosis of CD4+ CD8+ CD69+ thymocytes
|
|
• increased number of CD4+ CD8+ CD69+ and CD4+ CD8+ CD69- thymocytes in S and G2/M phase of cell cycle
|
| N |
• viable
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• decreased levels of T. muris specific serum IgG1 post-infection
|
|
• increased levels of T. muris?speciic serum IgG2a post-infection
|
|
• in the mesenteric lymph nodes of T. muris infected mice
|
|
• in the mesenteric lymph nodes of T. muris infected mice
|
|
• susceptible to T. muris infection, failing to clear parasites from the GI tract
|
|
• decreased levels of T. muris specific serum IgG1 post-infection
|
|
• increased levels of T. muris?speciic serum IgG2a post-infection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• surprisingly, mice show no evidence of thymic atrophy or any alterations in T cell development within the thymus
|
|
• mice show a mild reduction of T cells in spleen
• however, no alteration is observed in the phenotype of remaining T cells
|
|
• mice show a significant reduction of CD8-positive T cell number in spleen
|
| N |
• mice show no weight loss phenotype during the course of infection with Salmonella typhimurium
|
|
• mice show a mild reduction of T cells in spleen
• however, no alteration is observed in the phenotype of remaining T cells
|
|
• mice show a significant reduction of CD8-positive T cell number in spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice administered imiquimod (IMQ) to induce psoriasis show more severe acanthosis and dermal infiltrating cells than wild-type IMQ-administered mice
|
|
• mice administered IMQ exhibit more aggravated psoriasis compared to controls
|
|
• mice administered imiquimod (IMQ) to induce psoriasis show aggravation of psoriasis-like dermatitis compared to controls
|
|
• mice administered imiquimod (IMQ) to induce psoriasis show aggravation of psoriasis-like dermatitis compared to controls
|
|
• IMQ-administered mice show more evident splenomegaly than in IMQ-treated controls
|
|
• the proportion of Th1 cells are increased in splenic CD4+ T cells in IMQ-administered mice compared to controls
|
|
• the proportion of Th17 cells are increased in splenic CD4+ T cells in IMQ-administered mice compared to controls
• activated splenic naive CD4+ T cells show elevated Il17a and Il17f mRNA levels and naive CD4+ T cells cultured under Th17-polarizing conditions exhibit an increase in CD4+ IL-17A+ cells indicating promotion of Th17 cell differentiation
|
|
• the proportion of Th2 cells is decreased in splenic CD4+ T cells in IMQ-administered mice compared to controls
|
|
• mice administered imiquimod (IMQ) to induce psoriasis show aggravation of psoriasis-like dermatitis compared to controls
|
|
• IMQ-administered mice show more evident splenomegaly than in IMQ-treated controls
|
|
• the proportion of Th1 cells are increased in splenic CD4+ T cells in IMQ-administered mice compared to controls
|
|
• the proportion of Th17 cells are increased in splenic CD4+ T cells in IMQ-administered mice compared to controls
• activated splenic naive CD4+ T cells show elevated Il17a and Il17f mRNA levels and naive CD4+ T cells cultured under Th17-polarizing conditions exhibit an increase in CD4+ IL-17A+ cells indicating promotion of Th17 cell differentiation
|
|
• the proportion of Th2 cells is decreased in splenic CD4+ T cells in IMQ-administered mice compared to controls
|
|
• IMQ-administered mice show more evident splenomegaly than in IMQ-treated controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal double negative to double positive selection in the thymus
|
|
• in the spleen
|
|
• reduced peripheral naive T cells
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ T cells do not maintain survival in response to IL-7 unlike control cells
|
|
• in the spleen
|
|
• reduced peripheral naive T cells
|
|
• in the spleen
|
|
• in the spleen
|
|
• CD4+ T cells do not maintain survival in response to IL-7 unlike control cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• B220+ B cells are almost undetectable
• spleens often with reduced B cell counts
|
|
• both frequency and absolute numbers are increased
|
|
• significant decrease in total cell numbers for CD4+ cells
• significant decrease in naive CD4+ T cell numbers
|
|
• significant decrease in naive CD8+ T cell numbers
|
|
• splemomegaly at a young age
|
|
• unorganized or absent follicular structures in the spleen
|
|
• T cell areas of the spleen are unorganized, particularly those affecting CD8+ cells
|
|
• at a young age
|
|
• severe immune dysregulation
|
|
• increased activation of both CD4+ and CD8+ T cells
|
|
• increased activation of both CD4+ and CD8+ T cells
|
|
• B220+ B cells are almost undetectable
• spleens often with reduced B cell counts
|
|
• both frequency and absolute numbers are increased
|
|
• significant decrease in total cell numbers for CD4+ cells
• significant decrease in naive CD4+ T cell numbers
|
|
• significant decrease in naive CD8+ T cell numbers
|
|
• splemomegaly at a young age
|
|
• unorganized or absent follicular structures in the spleen
|
|
• T cell areas of the spleen are unorganized, particularly those affecting CD8+ cells
|
|
• splemomegaly at a young age
|
|
• increased activation of both CD4+ and CD8+ T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal thymocyte development
• T follicular helper cell frequency is similar to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
• weight does not reach control levels at 40-50 days and 60-75 days
|
|
|
• by day 44, mice develop enlarged spleen
|
|
• by day 44, thymus has reduced cellularity
|
|
|
• both CD8+ and CD4+ T cells show a reduced capacity to expand in response to CD3/CD28 stimulation
|
|
• by day 44, thymus has reduced cellularity
|
|
|
• by day 44, mice develop enlarged spleen
|
|
|
• mice exhibit a deficiency in T regulatory cells (CD4+, CD25+, FoxP3+)
|
|
|
• mice show prevention of the fatal systemic autoimmune and inflammatory disease that is seen in Foxp3sf/Y mice, with mice surviving at least up to 80 days and no presentation of scaly tails and ears, and no inflammation and tissue disruption at day 44
• values of total T cells return to normal and the accumulation of effector memory CD4+ and CD8+ T cells in the spleen that is seen in single Foxp3
|
|
|
• both CD8+ and CD4+ T cells show a reduced capacity to expand in response to CD3/CD28 stimulation
|
|
• by day 44, thymus has reduced cellularity
|
|
|
• by day 44, mice develop enlarged spleen
|
|
|
• mice exhibit a deficiency in T regulatory cells (CD4+, CD25+, FoxP3+)
|
|
|
• both CD8+ and CD4+ T cells show a reduced capacity to expand in response to CD3/CD28 stimulation
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 07/14/2026 MGI 6.24 |
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