T cell subset-specific susceptibility to aging

Marta Czesnikiewicz-Guzik, Won Woo Lee, Dapeng Cui, Yuko Hiruma, David L. Lamar, Zhi Zhang Yang, Joseph G. Ouslander, Cornelia M. Weyand, Jörg J. Goronzy

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356 Scopus citations

Abstract

With increasing age, the competence of the immune system to fight infections and tumors declines. Age-dependent changes have been mostly described for human CD8 T cells, raising the question of whether the response patterns for CD4 T cells are different. Gene expression arrays of memory CD4 T cells yielded a similar age-induced fingerprint as has been described for CD8 T cells. In cross-sectional studies, the phenotypic changes were not qualitatively different for CD4 and CD8 T cells, but occurred much more frequently in CD8 T cells. Homeostatic stability partially explained this lesser age sensitivity of CD4 T cells. With aging, naïve and central memory CD8 T cells were lost at the expense of phenotypically distinct CD8 effector T cells, while effector CD4 T cells did not accumulate. However, phenotypic shifts on central memory T cells were also more pronounced in CD8 T cells. This distinct stability in cell surface marker expression can be reproduced in vitro. The data show that CD8 T cells are age sensitive by at least two partially independent mechanisms: fragile homeostatic control and gene expression instability in a large set of regulatory cell surface molecules.

Original languageEnglish
Pages (from-to)107-118
Number of pages12
JournalClinical Immunology
Volume127
Issue number1
DOIs
StatePublished - Apr 2008

Bibliographical note

Funding Information:
This work was funded in part by grants from the National Institutes of Health (RO1 AG 15043 and RO1 AI 57266), the General Clinical Research Center (MO1 RR00039), the Noble Foundation, and the Aging Registry. The authors thank Tamela Yeargin for manuscript editing.

Keywords

  • Aging
  • CD4
  • CD8
  • CD85
  • Immunosenescence
  • Killer immunoglobulin-like receptors
  • T-cell homeostasis
  • T-cell subset

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