Tumor necrosis factor-alpha-induced apoptosis in T cells from aged humans: a role of TNFR-I and downstream signaling molecules.
Tumor necrosis factor-alpha (TNF-alpha) induces apoptosis predominantly via TNF-receptor I (TNF-RI). We have examined the molecular and biochemical pathways of TNF-alpha-induced apoptosis in T cells from aged and young subjects. Aged subjects show absolute lymphopenia and decreased numbers of both CD4+ and CD8+ T cells. T cells from aged subjects show increased sensitivity to TNF-alpha-induced apoptosis that is associated with increased expression of TNF-RI and decreased expression of TNF-RII in both CD4+ and CD8+ T cells. Agonistic TNF-RI also induced greater apoptosis in T cells from aged subjects as compared to young subjects, suggesting that increased TNF-alpha-induced apoptosis in aging is predominantly mediated via TNF-RI. There was an increased expression of FADD and increased activation of caspase 8 and caspase 3 in lymphocytes from aged humans as compared to young subjects. A role of impaired TNF-RII-mediated signaling in increased apoptosis in aged subjects is also discussed.
Gupta
Sudhir
S
Cellular and Molecular Immunology and Molecular Biology Laboratories, Division of Basic and Clinical Immunology, Department of Medicine, Medical Sciences 1, C-240, University of California, Irvine, CA 92697, USA. sgupta@uci.edu
D000375:Aging / Q000097:blood / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000494:pharmacology
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha