Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old

J Clin Immunol. 2003 Jul;23(4):247-57. doi: 10.1023/a:1024580531705.


Longitudinal studies suggest that a set of immune parameters including high percentages of peripheral CD8+, CD28-, CD57+ T lymphocytes, low CD4 and B cell counts, and poor T cell proliferative responses to mitogens is associated with decreased remaining longevity in the free-living very elderly (> 85 years). This combination of immune parameters was also significantly associated with an inverted CD4/CD8 ratio and cytomegalovirus seropositivity. Here, using tetramer technology, we show markedly increased numbers of CD8+ T cells bearing receptors for one single CMV epitope in the very elderly. Moreover, the fraction of these tetramer-reactive cells secreting interferon-gamma after specific antigenic stimulation was significantly lower in the old than in the young, as was the percentage of CD28-positive cells in this population. Therefore, we conclude that marked expansions of CMV-specific CD8+ T cells have occurred and that the obsession of a large fraction of the entire CD8+ T cell subset with one single viral epitope may contribute to the increased incidence of infectious disease in the elderly by shrinking the T cell repertoire available for responses to other antigens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Biomarkers
  • CD4-CD8 Ratio
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytomegalovirus / immunology*
  • Cytomegalovirus Infections / immunology*
  • Epitopes / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Longitudinal Studies
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell / analysis*
  • T-Lymphocyte Subsets / immunology


  • Biomarkers
  • Epitopes
  • Immunoglobulin G
  • Receptors, Antigen, T-Cell
  • Interferon-gamma