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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 superfamily, which is expressed on the surface of different types of cells. Cross-linking of CD95 leads to the induction of apoptosis. This may be of importance in many physiological systems, but seems to play a special 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 to the guidelines laid down in the Senieur protocol of the European Community'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 expressing cells. This increase was slower and less pronounced in old healthy subjects than in young ones. The activation-induced increase in CD95 expression was followed by a decrease, which was observed in both age groups, but was less pronounced in old subjects. Under long-term culture 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 was more pronounced in T cell lines derived from aged donors. The results suggest that a lowered sensitivity in the regulation of CD95 as well as an increased susceptibility to apoptosis-inducing mechanisms during clonal expansion are features of T cell senescence.