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

Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13694-9. doi: 10.1073/pnas.1107594108. Epub 2011 Aug 3.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology*
  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Proliferation
  • Cellular Senescence / immunology
  • HLA Antigens / immunology*
  • Homeostasis / immunology
  • Immunity / immunology
  • Immunologic Memory
  • Lymphocyte Count
  • Mice
  • Receptors, Antigen, T-Cell / immunology*

Substances

  • HLA Antigens
  • Receptors, Antigen, T-Cell