Apoptosis and ageing.
Stimulation of T cells from aged individuals leads to different kinds and/or size of responses if compared with the responses of T cells obtained from young individuals. In fact elderly is associated with a progressive decline of immune response besides an increasing incidence of autoimmune phenomena. These differences might be the result of modified 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 respect CD95 (Fas antigen) seems to play a major role in this course of events. In this study we show that just collected lymphocytes from old subjects displayed an increased expression of the apoptosis molecule CD95. The expression of CD95 and the spontaneous apoptosis showed the same trend. In fact the percentage of apoptotic cells in blood collected from old subjects was enhanced too. The lymphocyte subpopulation analysis by flow cytometry did not show significant changes in T subset percentages between old and young subjects. Moreover mononuclear cells obtained from aged individuals underwent apoptosis in culture in response to a single stimulation with mitogen or anti-CD3, more than mononuclear cells from young controls. To gain insight into mechanisms of this increased apoptosis, experiments were performed to evaluate the behaviors of lymphocytes from old and young donors in respect of interleukin-2 (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-CD3 and that this effect was not related to a different expression of CD95. Thus, during the course of ageing the different regulation of T cell homeostasis might be also explained by the modified proneness of lymphocytes to undergo apoptosis. The contemporaneous demonstration of a reduced Ca2+ influx in lymphoid cells of these subjects allows to suppose that multiple defects play a role in the pathogenesis of immunosenescence.
Istituto di Patologia generale dell'Università di Palermo, Italy.
M
M
Potestio
C
C
Caruso
F
F
Gervasi
G
G
Scialabba
C
C
D'Anna
G
G
Di Lorenzo
C R
CR
Balistreri
G
G
Candore
G C
GC
Romano
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D017209:Apoptosis; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D019014:fas Receptor / Q000096:biosynthesis
D019014:fas Receptor