SPECIFIC RESISTANCE OF T-CELLS TO CD95-INDUCED APOPTOSIS DURING S-PHASE OF THE CELL-CYCLE

We have examined the susceptibility of mouse thymocytes and Con A-acti vated mature T cells to CD95 (Fas; APO-l)-induced apoptosis at differe nt phases of the cell cycle. Signaling through CD95, induced by murine CD95 ligand expressed on fibroblasts, resulted in the preferential ap optosis of T cells in G(0)-G(1) phase of the cell cycle, T cells in S phase were selectively protected, CD95-induced apoptosis was inhibited by exogenous IL-2, which increases the percentage of cells in S phase , The inverse relationship between DNA synthesis and apoptosis in CD95 -ligated T cells was not observed during the spontaneous death of T ce lls in culture or during propriocidal apoptosis due to TCR cross-linki ng, to which cells in S phase were susceptible, These results show tha t in T cells there is no distinctively apoptosis-vulnerable phase of t he cell cycle; instead, apoptosis can occur at different phases of the cycle depending on the apoptotic stimulus.