mortality/aging
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• cachexic animals become moribund rapidly and are euthanized; by 6 months, 50% mortality in mutants is observed
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growth/size/body
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• moribund animals show complete loss of visceral adipose tissue
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• displayed by many animals at 4 months
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immune system
N |
• spleen and lymph nodes are not larger than controls despite T cell abnormalities
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• higher frequency of granulocytes in spleen and lymph nodes is observed
|
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• increase is detected in spleen and lymph nodes
|
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• significant increase in frequency of activated (CD62Llo44hi) CD4+ T cells is observed in spleen and lymph nodes
|
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• T lymphopenia in CD8+ compartment is observed
|
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• 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
|
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• 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
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• 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
|
hematopoietic system
|
• 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
|
adipose tissue
|
• moribund animals show complete loss of visceral adipose tissue
|
liver/biliary system
|
• infiltrating cells accumulate around most blood vessels in liver with additional foci in sinusoids
|
respiratory system
|
• infiltrating cells accumulate primarily around blood vessels, resulting in epithelial thickening of surrounding tissue
|
muscle
|
• moribund animals exhibit reduction in muscle mass
|
digestive/alimentary system
|
• small foci of inflammatory cells are more prevalent than in controls
|
endocrine/exocrine glands
|
• 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
|