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

H Tsukamoto, K Clise-Dwyer… - Proceedings of the …, 2009 - National Acad Sciences
H Tsukamoto, K Clise-Dwyer, GE Huston, DK Duso, AL Buck, LL Johnson, L Haynes
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
With age, T-cell generation from the thymus is much reduced, yet a substantial naïve T-cell
pool is maintained even in aged animals, suggesting that naïve T cells either persist longer
or turn over faster to maintain T-cell homeostasis. We found that with age, naïve CD4 T cells
became progressively longer-lived. Their longer lifespan did not depend on recognition of
self-peptide/class II. Newly generated naïve T cells derived from aged stem cells had a
shorter lifespan, like that of young naïve T cells. Conversely, naïve CD4 T cells derived from …
With age, T-cell generation from the thymus is much reduced, yet a substantial naïve T-cell pool is maintained even in aged animals, suggesting that naïve T cells either persist longer or turn over faster to maintain T-cell homeostasis. We found that with age, naïve CD4 T cells became progressively longer-lived. Their longer lifespan did not depend on recognition of self-peptide/class II. Newly generated naïve T cells derived from aged stem cells had a shorter lifespan, like that of young naïve T cells. Conversely, naïve 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 naïve T cells develop their longer lifespan during their sojourn in the periphery. Increased longevity of naïve CD4 T cells correlated well with reduced expression of proapoptotic molecule Bim. We suggest that the intrinsic increase in longevity helps maintain naïve T-cell homeostasis but facilitates the development of functional defects in mice.
National Acad Sciences