Nonrandom attrition of the naive CD8+ T-cell pool with aging governed by T-cell receptor:pMHC interactions

BD Rudd, V Venturi, G Li, P Samadder… - Proceedings of the …, 2011 - National Acad Sciences
BD Rudd, V Venturi, G Li, P Samadder, JM Ertelt, SS Way, MP Davenport, J Nikolich-Žugich
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
Immunity against new infections declines in the last quartile of life, as do numbers of naive T
cells. Peripheral maintenance of naive T cells over the lifespan is necessary because their
production drastically declines by puberty, a result of thymic involution. We report that this
maintenance is not random in advanced aging. As numbers and diversity of naive CD8+ T
cells declined with aging, surviving cells underwent faster rates of homeostatic proliferation,
were selected for high T-cell receptor: pMHC avidity, and preferentially acquired “memory …
Immunity against new infections declines in the last quartile of life, as do numbers of naive T cells. Peripheral maintenance of naive T cells over the lifespan is necessary because their production drastically declines by puberty, a result of thymic involution. We report that this maintenance is not random in advanced aging. As numbers and diversity of naive CD8+ T cells declined with aging, surviving cells underwent faster rates of homeostatic proliferation, were selected for high T-cell receptor:pMHC avidity, and preferentially acquired “memory-like” phenotype. These high-avidity precursors preferentially responded to infection and exhibited strong antimicrobial function. Thus, T-cell receptor avidity for self-pMHC provides a proofreading mechanism to maintain some of the fittest T cells in the otherwise crumbling naive repertoire, providing a degree of compensation for numerical and diversity defects in old T cells.
National Acad Sciences