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.