Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates

Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19960-5. doi: 10.1073/pnas.0705905104. Epub 2007 Dec 4.

Abstract

The loss of naïve T cells is a hallmark of immune aging. Although thymic involution is a primary driver of this naïve T cell loss, less is known about the contribution of other mechanisms to the depletion of naïve T cells in aging primates. We examined the role of homeostatic cycling and proliferative expansion in different T cell subsets of aging rhesus macaques (RM). BrdU incorporation and the expression of the G(1)-M marker Ki-67 were elevated in peripheral naïve CD4 and even more markedly in the naïve CD8 T cells of old, but not young adult, RM. Proliferating naïve cells did not accumulate in old animals. Rather, the relative size of the naïve CD8 T cell compartment correlated inversely to its proliferation rate. Likewise, T cell receptor diversity decreased in individuals with elevated naïve CD8 T cell proliferation. This apparent contradiction was explained by a significant increase in turnover concomitant with the naïve pool loss. The turnover increased exponentially when the naïve CD8 T cell pool decreased below 4% of total blood CD8 cells. These results link the shrinking naïve T cell pool with a dramatic increase in homeostatic turnover, which has the potential to exacerbate the progressive exhaustion of the naïve pool and constrict the T cell repertoire. Thus, homeostatic T cell proliferation exhibits temporal antagonistic pleiotropy, being beneficial to T cell maintenance in adulthood but detrimental to the long-term T cell maintenance in aging individuals.

Publication types

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

MeSH terms

  • Aging / immunology*
  • Animals
  • Cell Proliferation
  • Female
  • Homeostasis / immunology
  • Immunity, Innate / immunology*
  • Immunologic Memory / immunology
  • Ki-67 Antigen / metabolism
  • Kinetics
  • Macaca mulatta / immunology*
  • Male
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Ki-67 Antigen