TNF-alpha-induced apoptosis in human naïve and memory CD8+ T cells in aged humans.

Recently, human CD8+ T cells have been divided into naïve, central memory (T(CM)), and two types of effector memory cells (T(EM) and T(EMRA)), which are phenotypically identified by a set of cell surface molecules. In this investigation, we have compared the relative sensitivity of these subsets to TNF-alpha-induced apoptosis in young and aged humans. Our data show increased sensitivity of naïve and T(CM) CD8+ T cells from aged humans to TNF-alpha-induced apoptosis as compared to young subjects. Both T(EM) and T(EMRA) CD8+ T cells from young and aged subjects were relatively resistant to TNF-alpha-induced apoptosis and no significant difference was observed between young and aged subjects. Increased apoptosis of naïve and T(CM) CD8+ T cells in aged humans was associated with increased activation of caspase-8 and caspase-3 as compared to young subjects. There was no difference in the expression of TNFR-I or TNFR-II on any of the four subpopulations of CD8+ T cells between young and aged subjects. These data suggest that increased TNF-alpha-induced apoptosis of naïve and T(CM) CD8+ T cells may play a role in the deficiency of naïve and T(CM) CD8+ T cells in human aging. However, apoptosis does not appear to play a major role in increased accumulation of effector memory CD8+ T cells during human aging.