Cytotoxic effect of TNF and lymphotoxin on T lymphoblasts.
Recombinant TNF and lymphotoxin trigger the apoptotic death of normal mouse and human T lymphocyte blasts in vitro. This cytotoxic effect does not involve the Fas death pathway and differs from the TNF-triggered death of tumor cells in several respects: 1) It is a slower process, requiring 2 to 3 days; 2) it is blocked, rather than enhanced, by cycloheximide; and 3) based on the agonistic effect of anti-TNF receptor Abs, it involves a synergistic effect of both the 55-kDa TNFR1 and the 75-kDa TNFR2, as opposed to the dominance of TNFR1 for tumor cytotoxicity. The TNF-induced death of blasts is potently inhibited by IL-2, as well as by IL-1, IL-4, IFN-gamma, and IL-12. Because activated T cells secrete both TNF and LT, these findings reveal a new pathway for Ag-induced down-modulation of T cell responses.
Sarin
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Experimental Immunology Branch, NCI, National Institutes of Health, Bethesda, MD 20892, USA.
Conan-Cibotti
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Henkart
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PA
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008233:Lymphotoxin-alpha / Q000633:toxicity*; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D019014:fas Receptor / Q000502:physiology
D000961:Antilymphocyte Serum; D016207:Cytokines; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor