Costimulatory mechanisms in the elderly.

Aging is associated with the progressive increase of T cells that lack expression of the CD28 costimulatory molecule. Because CD28/B7 signal transduction is required for proliferation, T cells lacking CD28 gene expression are incapable of clonal expansion. To determine whether CD28- T cells are a separate lineage or, alternatively, are the progeny of formerly CD28+ T cells, we performed cell culture longitudinal analysis on the same population of T cells over time. Repeated antigen-induced T cell division ultimately leads to irreversible cell cycle arrest, shortened telomeres, loss of telomerase inducibility, and total absence of expression of CD28. This in vitro model has elucidated a novel facet of T cell biology that may explain the increased incidence of infection and cancer in the elderly.