Age-related susceptibility of naive and memory CD4 T cells to apoptosis induced by IL−2 deprivation or PHA addition

Abstract

The increased age-associated incidence of infectious and cancer diseases has been related to the alteration of immune functioning found in the elderly (immunosenescence). The reduction of naive T cells, which determine an impaired ability to mount immune responses to new antigens, represents a hallmark of the aging process. The aim of this study was to evaluate the susceptibility to apoptosis of purified naive and memory CD4(+) T cells from peripheral blood of healthy people ranging in age from 20 to 98 years. Two mechanisms of T cell elimination by apoptosis have been evaluated: cytokine deprivation and activation-induced cell death. After Interleukin-2 deprivation, the percentage of naive and memory CD4(+) apoptotic cells significantly increased with donor age concomitantly with a reduction of Bcl-2 expression and an increase of intracellular content of reactive oxygen species. After phytohemagglutinin addition, the percentage of apoptotic cells, the expression of CD95, and the intracellular reactive oxygen species, were not significantly correlated with age both in naive and memory CD4(+) T cells. Our data demonstrate the existence of functional alterations of naive and memory T cell populations during ageing. These alterations are mainly related to the mechanism of the apoptotic event rather than to the type of cell population involved (naive or memory). The alterations of naive and memory T cells may have implications in the age-related susceptibility to diseases.