Age-associated increase in lifespan of naive CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects

With age, T-cell generation from the thymus is much reduced, yet a substantial naive T-cell pool is maintained even in aged animals, suggesting that naive T cells either persist longer or turn over faster to maintain T-cell homeostasis. We found that with age, naive CD4 T cells became progressively longer-lived. Their longer lifespan did not depend on recognition of self-peptide/class II. Newly generated naive T cells derived from aged stem cells had a shorter lifespan, like that of young naive T cells. Conversely, naive CD4 T cells derived from middle-aged thymectomized mice were longer-lived in vivo, and their development of functional defects was accelerated. These observations suggest that naive T cells develop their longer lifespan during their sojourn in the periphery. Increased longevity of naive CD4 T cells correlated well with reduced expression of proapoptotic molecule Bim. We suggest that the intrinsic increase in longevity helps maintain naive T-cell homeostasis but facilitates the development of functional defects in mice.