Authors:
Brian D. Rudd, Vanessa Venturi, Gang Li, Partha Samadder, James M. Ertelt, Sing Sing Way, Miles P. Davenport, and Janko Nikolich-Žugich
Summary:
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.
Source:
Proceedings of the National Academy of Sciences of the United States of America; Vol. 108, No. 33, 13694-13699 (08/16/11)