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

Brian D. Rudd, Vanessa Venturi, Gang Li, Partha Samadder, James M. Ertelt, Sing Sing Way, Miles P. Davenport, Janko Nikolich-Žugich

Research output: Contribution to journalArticlepeer-review

112 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)13694-13699
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number33
StatePublished - Aug 16 2011


  • CD8 T cells
  • Lymphocyte homeostasis
  • T-cell repertoire

ASJC Scopus subject areas

  • General


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