DIFFERENTIAL ABILITY OF T-CELL SUBSETS TO UNDERGO ACTIVATION-INDUCED CELL-DEATH

Human T cell clones were analyzed for their susceptibility to activati on-induced cell death (AICD) in response to CD3/T cell receptor ligati on. AICD was observed only in Th1 clones and was Fas-mediated, whereas Th2 clones resisted AICD, Analysis of a panel of Th0 clones, characte rized by their ability to secrete both Th1 and Th2 cytokines, revealed that this subset included both AICD-sensitive (type A) and -resistant (type B) clones, Resistance to AICD by Th2 and Th0-type B clones was not due to lack of expression of either Fas receptor or its ligand, Pa radoxically, the AICD-resistant clones were susceptible to apoptosis w hen Fas receptor was directly ligated by anti-Fas antibodies, However, prior activation of the resistant clones by monoclonal antibodies to CD3/TCR complex induced resistance against Fas-mediated apoptosis, Thu s, the Fas-FasL pathway is critical for the induction of AICD in T cel ls, and moreover this pathway can be negatively regulated in the AICD- resistant clones by signals that are generated from ligation of the CD 3/TCR complex.