REGULATION OF CD95(APO-1) EXPRESSION AND THE INDUCTION OF APOPTOSIS IN HUMAN T-CELLS - CHANGES IN OLD-AGE

CD95 (APO-1) is a member of the TNF/nerve growth factor receptor super family, which is expressed on the surface of different types of cells. Cross-linking of CD95 leads to the induction of apoptosis. This may b e of importance in many physiological systems, but seems to play a spe cial role for the maintenance of immunological homeostasis. In view of the known decline of immune function in old age it seemed of interest to study the expression and inducibility of CD95 in peripheral blood T lymphocytes from young and old healthy subjects selected according t o the guidelines laid down in the Senieur protocol of the European Com munity's Concerted Action Programme on Aging. Resting T cells did not express CD95, T cell activation by anti-CD3 monoclonal antibody (OKT3) did, however, lead to a rapid increase in the number of CD95 expressi ng cells. This increase was slower and less pronounced in old healthy subjects than in young ones. The activation-induced increase in CD95 e xpression was followed by a decrease, which was observed in both age g roups, but was less pronounced in old subjects. Under long-term cultur e conditions T cell lines derived from both young and old individuals progressively lost the capacity to decrease the expression of CD95 at the end of their activation cycle and an increasing susceptibility to activation-driven programmed cell death was noted. The latter change w as more pronounced in T cell lines derived from aged donors. The resul ts suggest that a lowered sensitivity in the regulation of CD95 as wel l as an increased susceptibility to apoptosis-inducing mechanisms duri ng clonal expansion are features of T cell senescence.