digestive/alimentary system
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• increase in intestinal epithelial permeability indicating defective barrier function
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• mice develop spontaneous colitis
• mice in which gut commensal bacteria is removed by treatment with four antibiotics do not exhibit colitis
• -6-8 week old mutants transferred with TCRalphabeta+CD8alpha+ IELS show significant amelioration of colitis, however transfer with CD8+ T or natural killer cells has no effect on colitis
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hematopoietic system
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• drastic reduction in the frequency and absolute number of TCR beta+ T cells in the mesenteric lymph nodes
• however, the colonic lamina propria contains TCR beta+ T cells
• some mice have up to 10 times more T cells in colonic lamina propria than wild-type mice
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• the majority of TCR alpha beta+ T cells in the mesenteric lymph nodes and colonic lamina propria are CD4+ T cells compared to wild-type mice
• accumulation of CD4+ T cells in the colonic lamina propria
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• the TCR beta+NK1.1+ natural killer T cell population in the thymus and liver and alpha-GalCer/CD1d-reacted natural killer T cell population in the liver are hardly detectable in mice
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• reduction in the frequencies and absolute numbers of TCR beta+ intestinal intraepithelial lymphocytes (IEL) in both the small and large intestine
• both the CD8 alpha-alpha+ and CD8 alpha-beta+ cell populations of TCR beta+ IELs are almost completely absent
• the CD4+CD8 alpha-alpha+ cell population in TCR beta+CD8 beta- cells is decreased in the small and large intestine
• the colon exclusive TCR beta+CD4-CD8 alpha-CD8 beta- cell population is absent
• the remaining TCR beta+ IEL fraction is CD4+ T cells
• thymic IEL precursors (TCR alpha-beta+CD4-CD8-NK1.1-) are decreased in both frequency and absolute number; this reduction is due to almost complete loss of CD103+ cell population coexpressing both CD5 and CD122
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• increase in the frequency of TCR gamma-delta+ IELs in the small and large intestines and the absolute numbers of these IELs are increased in the colon but not the small intestine
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• frequency of regulatory T cells is higher in mesenteric lymph nodes and lower in colonic lamina propria in mice older than 10 weeks of age, however, absolute numbers of regulatory T cells are unchanged
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• reduction in frequency of CD25+Foxp3+ cells in CD4 single positive thymocytes of 10 week old mice that do not have colitis
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• thymic IEL precursors (TCRalphabeta+CD4-CD8-NK1.1-) stimulated with an agonistic anti-CD3 antibody in vitro do not show enlargement of cell size and induced expression of CD25, IL-2Ralpha chain as seen in wild-type cells
• thymic IEL precursors treated with the agonistic anti-CD3 antibody show inefficient induction of CD8alpha induction
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• CD4+ T cells from colonic lamina propria and mesenteric lymph nodes stimulated with PMA plus ionomycin exhibit a more robust production of IFN-gamma and IL-17A than in wild-type cells
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• in an in vitro suppression assay, regulatory T cells show less suppressive activity than wild-type T cells, indicating failure of suppressive function of the leaky regulatory T cells
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homeostasis/metabolism
immune system
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• mice develop spontaneous colitis
• mice in which gut commensal bacteria is removed by treatment with four antibiotics do not exhibit colitis
• -6-8 week old mutants transferred with TCRalphabeta+CD8alpha+ IELS show significant amelioration of colitis, however transfer with CD8+ T or natural killer cells has no effect on colitis
|
|
• drastic reduction in the frequency and absolute number of TCR beta+ T cells in the mesenteric lymph nodes
• however, the colonic lamina propria contains TCR beta+ T cells
• some mice have up to 10 times more T cells in colonic lamina propria than wild-type mice
|
|
• the majority of TCR alpha beta+ T cells in the mesenteric lymph nodes and colonic lamina propria are CD4+ T cells compared to wild-type mice
• accumulation of CD4+ T cells in the colonic lamina propria
|
|
• the TCR beta+NK1.1+ natural killer T cell population in the thymus and liver and alpha-GalCer/CD1d-reacted natural killer T cell population in the liver are hardly detectable in mice
|
|
• reduction in the frequencies and absolute numbers of TCR beta+ intestinal intraepithelial lymphocytes (IEL) in both the small and large intestine
• both the CD8 alpha-alpha+ and CD8 alpha-beta+ cell populations of TCR beta+ IELs are almost completely absent
• the CD4+CD8 alpha-alpha+ cell population in TCR beta+CD8 beta- cells is decreased in the small and large intestine
• the colon exclusive TCR beta+CD4-CD8 alpha-CD8 beta- cell population is absent
• the remaining TCR beta+ IEL fraction is CD4+ T cells
• thymic IEL precursors (TCR alpha-beta+CD4-CD8-NK1.1-) are decreased in both frequency and absolute number; this reduction is due to almost complete loss of CD103+ cell population coexpressing both CD5 and CD122
|
|
• increase in the frequency of TCR gamma-delta+ IELs in the small and large intestines and the absolute numbers of these IELs are increased in the colon but not the small intestine
|
|
• frequency of regulatory T cells is higher in mesenteric lymph nodes and lower in colonic lamina propria in mice older than 10 weeks of age, however, absolute numbers of regulatory T cells are unchanged
|
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• reduction in frequency of CD25+Foxp3+ cells in CD4 single positive thymocytes of 10 week old mice that do not have colitis
|
|
• thymic IEL precursors (TCRalphabeta+CD4-CD8-NK1.1-) stimulated with an agonistic anti-CD3 antibody in vitro do not show enlargement of cell size and induced expression of CD25, IL-2Ralpha chain as seen in wild-type cells
• thymic IEL precursors treated with the agonistic anti-CD3 antibody show inefficient induction of CD8alpha induction
|
|
• CD4+ T cells from colonic lamina propria and mesenteric lymph nodes stimulated with PMA plus ionomycin exhibit a more robust production of IFN-gamma and IL-17A than in wild-type cells
|
|
• in an in vitro suppression assay, regulatory T cells show less suppressive activity than wild-type T cells, indicating failure of suppressive function of the leaky regulatory T cells
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• colons show increased mRNA levels of proinflammatory cytokines and RegIII-beta/gamma proteins (antimicrobial peptides)
• elevation of expression of IFN-gamma and IL-17
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• CD4+ T cells from colonic lamina propria and mesenteric lymph nodes stimulated with PMA plus ionomycin exhibit a more robust production of IFN-gamma than in wild-type cells
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• CD4+ T cells from colonic lamina propria and mesenteric lymph nodes stimulated with PMA plus ionomycin exhibit a more robust production of IL-17A than in wild-type cells
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liver/biliary system
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• large numbers of bacteria are detected in the livers
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