|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced CD4+CD8int intermediate cells
|
|
• reduced CD4+CD8int intermediate cells
|
|
• reduced CD4+CD8int intermediate cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced numbers of total thymocytes
|
|
• in an in vitro assay, mutant thymocytes underwent OCA peptide 257-264 dependent cell death more readily than control, indicating enhanced negative selection
|
|
• lower proportions of double-positive and single-positive cells, and reduced CD8 SP cell in the peripheral T cell population, both indicating impaired positive selection
|
|
• reduced numbers of total thymocytes
|
|
• in an in vitro assay, mutant thymocytes underwent OCA peptide 257-264 dependent cell death more readily than control, indicating enhanced negative selection
|
|
• lower proportions of double-positive and single-positive cells, and reduced CD8 SP cell in the peripheral T cell population, both indicating impaired positive selection
|
|
• reduced numbers of total thymocytes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• tamoxifen-treated mice exhibit increased serum alanine transaminase levels compared with un-induced mice
• however, un-induced mice exhibit normal alanine transaminase levels
|
|
|
| ♀ | 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 |
|
• 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 kill B16 cells pulsed with OVA peptide 257-264 less effectively than control CD8 T cells
|
|
• CD8 T cells stimulated with T cell lymphoma cell line EL-4 transfected with Pvr and pulsed with OVA peptide 257-264 fail to become activated
|
|
• in CD8 T cells stimulated with T cell lymphoma cell line EL-4 transfected with murine Pvr and pulsed with OVA peptide 257 ? 264
• however, proliferation in response to dendritic cell stimulation is similar to wild-type
|
|
• CD8 T cells kill B16 cells pulsed with OVA peptide 257-264 less effectively than control CD8 T cells
|
|
• CD8 T cells stimulated with T cell lymphoma cell line EL-4 transfected with Pvr and pulsed with OVA peptide 257-264 fail to become activated
|
|
• in CD8 T cells stimulated with T cell lymphoma cell line EL-4 transfected with murine Pvr and pulsed with OVA peptide 257 ? 264
• however, proliferation in response to dendritic cell stimulation is similar to wild-type
|
|
• fewer IFN gamma secreting T cells are evident in lymph nodes after restimulation with the T cell lymphoma cell line EL-4 cells transfected with Pvr and pulsed with OVA peptide 257-264
• however, the frequency of IFN gamma secreting cells is similar to wild-type after restimulation with dendritic cells
|
|
• in CD8 T cells stimulated with T cell lymphoma cell line EL-4 transfected with murine Pvr and pulsed with OVA peptide 257 ? 264
• however, proliferation in response to dendritic cell stimulation is similar to wild-type
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced persistence of CD8alphaloCD11ahi cells
|
|
• IFN-gamma producing cells are reduced at 7 days after infection and pulse with OVA
|
|
• reduced persistence of CD8alphaloCD11ahi cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• adoptive transfer studies indicate that there is impaired accumulation of effector CD8+ T cells possibly because of an increase in apoptosis in these cells with surviving cells developing a central memory-like phenotype
|
|
• adoptive transfer studies indicate that there is impaired accumulation of effector CD8+ T cells possibly because of an increase in apoptosis in these cells with surviving cells developing a central memory-like phenotype
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• in the periphery
|
|
• in the thymus
• in the periphery
|
|
• in the periphery
|
|
• in the thymus
• in the periphery
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• the altered CD8+ T cell development that generates a large proportion of memory T cells in Itktm1Ljb homozygotes does not occur in these mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 30% reduction of CD8+ cells in the thymus
• reductions particularly involve cells expressing transgene coded TCR
• no alterations in CD4+ T cell
|
|
• 30% reduction of CD8+ cells in the thymus
• reductions particularly involve cells expressing transgene coded TCR
• no alterations in CD4+ T cell
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• include a much higher percentage of CD4 SP cells and a correspondingly smaller CD8 SP population
|
|
• include a much higher percentage of CD4 SP cells and a correspondingly smaller CD8 SP population
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• OVA-specific CD8 T cells make up 97% of cells found in lymph nodes and 24% of cells in spleen
|
|
• many of the CD4 T cells express the transgenic TCR alpha chain
|
|
• CD4 T cells make up less than 1% of total cells found in lymph nodes or spleen
|
|
• OVA-specific CD8 T cells make up 97% of cells found in lymph nodes and 24% of cells in spleen
|
|
• many of the CD4 T cells express the transgenic TCR alpha chain
|
|
• CD4 T cells make up less than 1% of total cells found in lymph nodes or spleen
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• purified CD4+ and CD8+ T cells respectively, showed a significant reduction in IFNG and IL-2 protein levels and decreased proliferation in response to stimulation
|
|
• purified CD4+ and CD8+ T cells respectively, showed a significant reduction in IFNG and IL-2 protein levels and decreased proliferation in response to stimulation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice show normal T cell development, including normal positive selection
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• impaired adhesion to wild-type B cells when stimulated with ovalbumin
• however, T cells exhibit increased adhesion to and normal killing of B cells lacking Slamf6 (Sh2d1atm1Pls)
|
|
• in cytotoxic T cells stimulated with ovalbumin
|
|
• impaired adhesion to wild-type B cells when stimulated with ovalbumin
• however, T cells exhibit increased adhesion to and normal killing of B cells lacking Slamf6 (Sh2d1atm1Pls)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• double-negative thymocytes are allowed to progress to double- and single-positive stages, indicating defective negative selection
|
|
• also observed to be defective
|
|
• female mice have increased numbers of CD4+CD8- T cells not expressing the transgene in the lymph node and thymus
• male mutants also show skewing toward CD4+ lineage
|
|
• female mice have substantially reduced numbers of CD4-CD8+ H-Y TCR+ cells in thymus and periphery compared to controls
|
| N |
• male mutants have normal-sized thymuses, whereas Tapbp-sufficient, transgenic males have a small thymus
|
|
• double-negative thymocytes are allowed to progress to double- and single-positive stages, indicating defective negative selection
|
|
• also observed to be defective
|
|
• female mice have increased numbers of CD4+CD8- T cells not expressing the transgene in the lymph node and thymus
• male mutants also show skewing toward CD4+ lineage
|
|
• female mice have substantially reduced numbers of CD4-CD8+ H-Y TCR+ cells in thymus and periphery compared to controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymocytes fail to exit the CD4hiCD8int stage to the CD8 single-positive stage
|
|
• the proportion and number of double-positive thymocytes is greater than controls
|
|
• very few single-positive thymocytes are generated in the thymus
|
|
• thymocytes fail to exit the CD4hiCD8int stage to the CD8 single-positive stage
|
|
• the proportion and number of double-positive thymocytes is greater than controls
|
|
• very few single-positive thymocytes are generated in the thymus
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• T cells exhibit normal adhesion to wild-type B cells and B cells lacking Slamf6 (Sh2d1atm1Pls)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice do not develop lymphoid tumors, but present after a long latency with gastrointestinal stromal tumors
|
|
• mice present after a long latency with hepatocellular carcinomas and sarcomas
|
|
• mice present after a long latency with hepatocellular carcinomas and sarcomas
|
|
• mice do not develop lymphoid tumors, but present after a long latency with gastrointestinal stromal tumors
|
|
• mice present after a long latency with hepatocellular carcinomas and sarcomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 12 days after immunization in an adoptive transfer experiment, the number of T cells in the spleen, lymph nodes, lung, liver, and bone marrow are reduced compared with wild-type cells
|
|
• fewer CD8+ T cells respond to antigen-cross presentation by CD8+ dendritic cells compared to in wild-type mice
|
|
• 12 days after immunization in adoptive transfer experiments
|
|
• immunized T cells produce less IFN-gamma on day 12 compared with similarly treated wild-type cells
|
|
• 12 days after immunization in an adoptive transfer experiment, the number of T cells in the spleen, lymph nodes, lung, liver, and bone marrow are reduced compared with wild-type cells
|
|
• fewer CD8+ T cells respond to antigen-cross presentation by CD8+ dendritic cells compared to in wild-type mice
|
|
• 12 days after immunization in adoptive transfer experiments
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• population is lower than in Mapk1-deficient mice with Tg(CD4-cre)1Cwi or with transgene and Mapk3 deficiency
|
|
• population is lower than in Mapk1-deficient mice with Tg(CD4-cre)1Cwi or with transgene and Mapk3 deficiency
|
|
• population is lower than in Mapk1-deficient mice with Tg(CD4-cre)1Cwi or with transgene and Mapk3 deficiency
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the thymus is smaller than normal
|
|
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR
|
|
• decreased number of CD8 T cells are found in both the thymus and in the periphery
|
|
• the thymus is smaller than normal
|
|
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR
|
|
• decreased number of CD8 T cells are found in both the thymus and in the periphery
|
|
• the thymus is smaller than normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the thymus is smaller than normal
|
|
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR
|
|
• decreased number of CD8 T cells are found in both the thymus and in the periphery
|
|
• the thymus is smaller than normal
|
|
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR
|
|
• decreased number of CD8 T cells are found in both the thymus and in the periphery
|
|
• the thymus is smaller than normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• transgenic CD8+ thymocytes are not fully mature
|
|
• positive selection of CD4 and CD8 lineage is diminished
|
|
• transgenic CD8+ thymocytes are not fully mature
|
|
• positive selection of CD4 and CD8 lineage is diminished
|
|
• transgenic CD8+ thymocytes are not fully mature
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8+ T cells from these mutant mice induce diabetes as early as 6 days after transfer into Tg(Ins2-TFRC/OVA)296Wehi transgenic mice that express OVA in insulin-producing cells
• 60% of transgenic mice develop diabetes and almost all mice have invasive insulitis compared to transgenic mice receiving wild-type OT-I cells where 60% of mice display no disease
• mutant OT-I T cells found in the pancreatic lymph nodes have twice as much proliferation as controls 50 hours after transfer compared to transferred wild-type OT-I T cells
• two weeks after transfer, there are twice as many mutant OT-I T cells in pancreatic lymph nodes compared to wild-type OT-I T cells controls
• thus, mutant autoreactive OT-I CD8+ T cells are resistant to tolerance induction mechanisms that limit the expansion of autoreactive
CD8 + T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal MHC class-specific T cell development
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the transgenic TCR does not have a high affinity for the H2-Kbm1 allele leading to poor selection of T cell precursors for the CD8 single positive subset
|
|
• the transgenic TCR does not have a high affinity for the H2-Kbm1 allele leading to poor selection of T cell precursors for the CD8 single positive subset
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the transgenic TCR is positively selected for on this genetic background based on the high expression of TCR on peripheral CD8 T cells
|
|
• the transgenic TCR is positively selected for on this genetic background based on the high expression of TCR on peripheral CD8 T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• strong decrease in the population of DP cells expressing high levels of CD4 and CD8 with thymocytes accumulating at intermediate stages of differentiation from DP to CD8 single positive
• thymocytes accumulate at the DP3 stage
|
|
• thymocytes accumulate at intermediate stages of differentiation from DP to CD8 single positive indicating a partial arrest beyond the positive selection checkpoint
• thymocytes accumulate at the DP3 stage
• partial arrest at the DN3 stage
|
|
• expression analysis indicates a defect in positive selection
|
|
• strong decrease in the population of DP cells expressing high levels of CD4 and CD8
|
|
• decrease in the absolute number of thymocytes
|
|
• strong decrease in the population of DP cells expressing high levels of CD4 and CD8 with thymocytes accumulating at intermediate stages of differentiation from DP to CD8 single positive
• thymocytes accumulate at the DP3 stage
|
|
• thymocytes accumulate at intermediate stages of differentiation from DP to CD8 single positive indicating a partial arrest beyond the positive selection checkpoint
• thymocytes accumulate at the DP3 stage
• partial arrest at the DN3 stage
|
|
• expression analysis indicates a defect in positive selection
|
|
• decrease in the absolute number of thymocytes
|
|
• strong decrease in the population of DP cells expressing high levels of CD4 and CD8
|
|
• strong decrease in the population of DP cells expressing high levels of CD4 and CD8 with thymocytes accumulating at intermediate stages of differentiation from DP to CD8 single positive
• thymocytes accumulate at the DP3 stage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adoptive transfer, T cells induce rapid onset of diabetes in RIP-ovahigh recipients within 1 to 3 weeks unlike similarly treated wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• following adoptive transfer, naive CD8+ T cells exhibit no proliferation in RIP-ovalow recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, T cells exhibit increased cell intrinsic proliferation in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, CD8+ T cells induce peri-ductal infiltrates and vasculitis within the pancreas in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, CD8+ T cells induce severe insulitis in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, CD8+ T cells fail to undergo cross-tolerization when transplanted into RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, CD8+ T cells induce diabetes in RIP-ovahigh or RIP-ovalow recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, CD8+ T cells induce vasculitis within the pancreas in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, CD8+ T cells induce peri-ductal infiltrates and vasculitis within the pancreas in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, CD8+ T cells induce severe insulitis in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, naive CD8+ T cells exhibit no proliferation in RIP-ovalow recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, T cells exhibit increased cell intrinsic proliferation in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, naive CD8+ T cells exhibit no proliferation in RIP-ovalow recipients unlike similarly treated wild-type cells
|
|
• following adoptive transfer, T cells exhibit increased cell intrinsic proliferation in RIP-ovahigh recipients unlike similarly treated wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• population is lower than in Mapk1-deficient mice with Tg(CD4-cre)1Cwi or with transgene and Mapk3 deficiency
|
|
• population is lower than in Mapk1-deficient mice with Tg(CD4-cre)1Cwi or with transgene and Mapk3 deficiency
|
|
• population is lower than in Mapk1-deficient mice with Tg(CD4-cre)1Cwi or with transgene and Mapk3 deficiency
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• naive CD8+ T cell activation, proliferation, and differentiation are normal
|
|
• following adoptive transfer into wild-type mice and infection with VV-OVA, CD8+ T cells exhibit defective migration into the peritoneum after 8 days compared to when wild-type cells are transferred into a similarly treated host
• however, 4 days after infection CD8+ T cell numbers are normal
|
|
• following adoptive transfer into wild-type mice and infection with VV-OVA, CD8+ T cells exhibit defective migration into the peritoneum after 8 days compared to when wild-type cells are transferred into a similarly treated host
• however, 4 days after infection CD8+ T cell numbers are normal
|
|
• following adoptive transfer into wild-type mice and infection with VV-OVA, CD8+ T cells exhibit defective migration into the peritoneum after 8 days compared to when wild-type cells are transferred into a similarly treated host
• however, 4 days after infection CD8+ T cell numbers are normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the thymus is smaller than normal
|
|
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR
|
|
• decreased number of CD8 T cells are found in both the thymus and in the periphery
|
|
• the thymus is smaller than normal
|
|
• the transgenic TCR is negatively selected on this genetic background based on the small number of CD8 T cells found in the periphery that express the transgenic TCR
|
|
• decreased number of CD8 T cells are found in both the thymus and in the periphery
|
|
• the thymus is smaller than normal
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• T cells exhibit normal adhesion to wild-type B cells and B cells lacking Slamf6 (Sh2d1atm1Pls)
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• doubly transgenic mice begin to exhibit glucosuria as early as 20 days of age; by 70 days, all the mice have urine glucose concentrations greater than 15 mM
|
|
• doubly transgenic mice begin to exhibit glucosuria as early as 20 days of age; by 70 days, all the mice have urine glucose concentrations greater than 15 mM
|
|
• histological examination of 5 doubly transgenic mice aged 5-68 days revealed heavy lymphocyte infiltration of the pancreatic islets of all mice; 82% of islets, on average, were infiltrated
|
|
• severe depletion of beta cells in infiltrated islets of the five mice examined
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• T cells exhibit decreased antigen detection efficiency compared with wild-type cells
|
|
• T cells exhibit decreased antigen detection efficiency compared with wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduced T cell expansion in response to antigen with a higher percentage of terminal effector CD8 cells and lower development of memory T cells
|
|
• reduced T cell expansion in response to antigen with a higher percentage of terminal effector CD8 cells and lower development of memory T cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• after administration of OVA peptide 257-264 has no affect on mortality
|
| N |
• no morphological abnormalities or increased apoptosis after administration of OVA peptide 257-264
|
|
• extensive infiltration of Valpha2+ CD8+ lymphocytes after administration of OVA peptide 257-264
|
|
• extensive infiltration of Valpha2+ CD8+ lymphocytes after administration of OVA peptide 257-264
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• means survival of 181 days
|
|
• mice exposed to MHV-OVA develop heptoacellular carcinomas and sarcomas
|
|
• mice develop ALK+ lymphomas, with a peripheral rather than thymic presentation
• tumors show cells with eosinophilic cytoplasm and reniform nuclei, resembling the classic hallmark cells of human anaplastic large cell lymphoma
• tumors do not show endogenous TCRbeta rearrangements
• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development
|
|
• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development and develop hepatocellular carcinomas and sarcomas
|
|
• mice exposed to MHV-OVA develop heptoacellular carcinomas and sarcomas
|
|
• mice exposed to MHV-OVA develop heptoacellular carcinomas and sarcomas
|
|
• total thymic cellularity is increased
• however, mice have normal T-cell development profiles
|
|
• mice develop ALK+ lymphomas, with a peripheral rather than thymic presentation
• tumors show cells with eosinophilic cytoplasm and reniform nuclei, resembling the classic hallmark cells of human anaplastic large cell lymphoma
• tumors do not show endogenous TCRbeta rearrangements
• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development
|
|
• total thymic cellularity is increased
• however, mice have normal T-cell development profiles
|
|
• increase in cellular proliferation of the DN3 population
|
|
• total thymic cellularity is increased
• however, mice have normal T-cell development profiles
|
|
• increase in cellular proliferation of the DN3 population
|
|
• mice exposed to MHV-OVA show abrogated anaplastic large cell lymphoma development and develop hepatocellular carcinomas and sarcomas
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• development of B16.MO5 tumors engineered to express OVA is delayed relative to control mice
• ovalbumin mRNA is not present in tumors although it is present in control tumors
• ovalbumin expression is restored in tumor cells when re-isolated and cultured
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• CD8 single positive T cells of the thymus proliferate vigorously in response to OVA peptide in the context of H2-Kb
|
|
• when OVA peptide is included in fetal thymic organ culture, almost all double-positive T cells are clonally deleted as a result of negative selection
|
|
• the transgenic T cell receptor (TCR) has high affinity for the H2-Kb allele that leads to increased positive selection of T cell precursors for the CD8 T cell lineage
(J:92867)
• the transgenic TCR is positively selected for on this genetic background based on high expression of the TCR on peripheral CD8 T cells
(J:133645)
|
|
• there is significant skewing in the CD4:CD8 ratio of the thymus towards CD8 single positive T cells
(J:92867)
• the ratio of CD4- to CD8- T cells in the periphery is strongly skewed to CD8 T cells
(J:133645)
|
|
• there is approximately a 7-fold reduction in the number of CD4 T cells in the spleen and lymph nodes of 9 week old mice
• there is almost a 5-fold decrease in the percentage of single positive CD4 T cells found in the thymus
|
|
• all CD8 single positive T cells in the thymus express the transgenic TCR that is specific for OVA peptide in the context of H2-Kb
• the CD8 single positive T cells in the thymus express high levels of the transgenic TCR
|
|
• CD8 T cells make up 20% of the total number of cells in the thymus
(J:92867)
• there is about a 2-fold increase in the number of CD8 T cells in the spleen and lymph nodes of 9 week old mice
(J:133645)
• OVA-specific CD8 T cells make up 50% of the cells found in lymph nodes
(J:133645)
• there is over a 6-fold increase in the percentage of single positive CD8 T cells found in the thymus
(J:133645)
|
|
• CD8 T cells have high cytolytic activity toward target cells containing OVA peptide
(J:92867)
• activated CD8 T cells are strongly cytolytic to cells containing OVA peptide
(J:133645)
|
|
• CD8 single positive T cells of the thymus proliferate vigorously in response to OVA peptide in the context of H2-Kb
|
|
• when OVA peptide is included in fetal thymic organ culture, almost all double-positive T cells are clonally deleted as a result of negative selection
|
|
• the transgenic T cell receptor (TCR) has high affinity for the H2-Kb allele that leads to increased positive selection of T cell precursors for the CD8 T cell lineage
(J:92867)
• the transgenic TCR is positively selected for on this genetic background based on high expression of the TCR on peripheral CD8 T cells
(J:133645)
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• there is significant skewing in the CD4:CD8 ratio of the thymus towards CD8 single positive T cells
(J:92867)
• the ratio of CD4- to CD8- T cells in the periphery is strongly skewed to CD8 T cells
(J:133645)
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• there is approximately a 7-fold reduction in the number of CD4 T cells in the spleen and lymph nodes of 9 week old mice
• there is almost a 5-fold decrease in the percentage of single positive CD4 T cells found in the thymus
|
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• all CD8 single positive T cells in the thymus express the transgenic TCR that is specific for OVA peptide in the context of H2-Kb
• the CD8 single positive T cells in the thymus express high levels of the transgenic TCR
|
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• CD8 T cells make up 20% of the total number of cells in the thymus
(J:92867)
• there is about a 2-fold increase in the number of CD8 T cells in the spleen and lymph nodes of 9 week old mice
(J:133645)
• OVA-specific CD8 T cells make up 50% of the cells found in lymph nodes
(J:133645)
• there is over a 6-fold increase in the percentage of single positive CD8 T cells found in the thymus
(J:133645)
|
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• CD8 T cells have high cytolytic activity toward target cells containing OVA peptide
(J:92867)
• activated CD8 T cells are strongly cytolytic to cells containing OVA peptide
(J:133645)
|
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• CD8 single positive T cells of the thymus proliferate vigorously in response to OVA peptide in the context of H2-Kb
|
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased mortality after administration of OVA peptide 257-264
|
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• extensive apoptosis develops after administration of OVA peptide 257-264
• extensive cell death
|
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• extensive infiltration of Valpha2+ CD8+ lymphocytes after administration of OVA peptide 257-264
• CD8+ lymphocytes spike 3 days after administration of OVA peptide 257-264
|
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• become pale and friable by the second day after administration of OVA peptide 257-264
|
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• extensive infiltration of Valpha2+ CD8+ lymphocytes after administration of OVA peptide 257-264
• CD8+ lymphocytes spike 3 days after administration of OVA peptide 257-264
|
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• increased mortality after administration of OVA peptide 257-264
|
|
• extensive apoptosis develops after administration of OVA peptide 257-264
• extensive cell death
|
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 04/30/2024 MGI 6.23 |
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