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

Proc Natl Acad Sci U S A. 2009 Oct 27;106(43):18333-8. doi: 10.1073/pnas.0910139106. Epub 2009 Oct 8.

Abstract

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.

Publication types

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

MeSH terms

  • Aging*
  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Bcl-2-Like Protein 11
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Survival
  • Histocompatibility Antigens / immunology
  • Homeostasis*
  • Immunity, Innate*
  • Membrane Proteins / metabolism
  • Mice
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • Thymectomy

Substances

  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Histocompatibility Antigens
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell