LAUSR

As the thymus involutes during aging, the T-cell pool has to be maintained by the periodic expansion of preexisting T cells during adulthood. A conundrum is that repeated episodes of activation and proliferation drive the differentiation of T cells toward replicative senescence, due to telomere erosion. This review discusses mechanisms that regulate the end-stage differentiation (senescence) of T cells. Although these cells, within both CD4 and CD8 compartments, lose proliferative activity after antigen-specific challenge, they acquire innate-like immune function. While this may confer broad immune protection during aging, these senescent T cells may also cause immunopathology, especially in the context of excessive inflammation in tissue microenvironments.