Activated CD8(+) T cells from aged mice exhibit decreased activation-induced cell death

To uncouple the defects of activation and apoptosis of T cells from aged mi ce, we used anti-CD3 plus IL-2 stimulation to induce an activation response and analyzed the subsequent activation-induced cell death (AICD) response of T cells from 16-month-old mice. The results herein demonstrate that T ce lls from 16-month-old mice could be activated by anti-CD3-induced activatio n signals but exhibited distinct phenotypic and functional features compare d to young (2-month-old) mice. These include a decrease in AICD, a delayed entry into the cell cycle, and a decreased telomerase activity. The decreas ed AICD of T cells from 16-month-old mice is associated with a decreased ex pression of Fas and Fas ligand (FasL), decreased susceptibility to anti-Fas -induced apoptosis, and an increased expansion of a CD8(+) T-cell populatio n. Prior to activation, these T cells exhibit a phenotype that is CD44(hi)C D62L(hi). After stimulation, these T cells produced high levels of the pro- inflammatory cytokine, IFN-gamma, and developed an increased population of IFN-gamma +IFN-gammaR-T cells. Our results suggest that there is a dysregul ation in T-cell homeostasis in aged mice associated with a decrease in AICD of CD8(+) T cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reser ved.