TNF-alpha controls intrahepatic T cell apoptosis and peripheral T cell numbers.
At the end of an immune response, activated lymphocyte populations contract, leaving only a small memory population. The deletion of CD8(+) T cells from the periphery is associated with an accumulation of CD8(+) T cells in the liver, resulting in both CD8(+) T cell apoptosis and liver damage. After adoptive transfer and in vivo activation of TCR transgenic CD8(+) T cells, an increased number of activated CD8(+) T cells was observed in the lymph nodes, spleen, and liver of mice treated with anti-TNF-alpha. However, caspase activity was decreased only in CD8(+) T cells in the liver, not in those in the lymphoid organs. These results indicate that TNF-alpha is responsible for inducing apoptosis in the liver and suggest that CD8(+) T cells escaping this mechanism of deletion can recirculate into the periphery.
Murray
Debbie A
DA
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, University of Rochester, Rochester, NY 14642, USA.
Crispe
I Nicholas
IN
D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D014409:Tumor Necrosis Factor-alpha