APOPTOSIS AND AGING

Stimulation of T cells from aged individuals leads to different kinds and/or size of responses if compared with the responses of T cells obt ained from young individuals. In fact elderly is associated with a pro gressive decline of immune response besides an increasing incidence of autoimmune phenomena. These differences might be the result of modifi ed cellular mechanisms controlling the immune system in the course of ageing. The apoptotic deletion of activated T cells has been proposed as the key mechanism to maintain T cell homeostasis, and in this respe ct CD95 (Fas antigen) seems to play a major role in this course of eve nts, In this study we show that just collected lymphocytes from old su bjects displayed an increased expression of the apoptosis molecule CD9 5. The expression of CD95 and the spontaneous apoptosis showed the sam e trend. In fact the percentage of apoptotic cells in blood collected from old subjects was enhanced too. The lymphocyte subpopulation analy sis by flow cytometry did not show significant changes in T subset per centages between old and young subjects. Moreover mononuclear cells ob tained from aged individuals underwent apoptosis in culture in respons e to a single stimulation with mitogen or anti-CD3, more than mononucl ear cells from young controls. To gain insight into mechanisms of this increased apoptosis, experiments were performed to evaluate the behav iors of lymphocytes from old and young donors in respect of interleuki n-a (IL-2) rescue from apoptosis. Results show that IL-2 rescued only a little fraction of cells of old donors from apoptosis when activated by anti-CDS and that this effect was not related to a different expre ssion of CD95. Thus, during the course of ageing the different regulat ion of T cell homeostasis might be also explained by the modified pron eness of lymphocytes to undergo apoptosis. The contemporaneous demonst ration of a reduced Ca2+ influx in lymphoid cells of these subjects al lows to suppose that multiple defects play a role in the pathogenesis of immunosenescence. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.