Age-related CD8 T cell clonal expansions constrict CD8 T cell repertoire and have the potential to impair immune defense

Ilhem Messaoudi, Joël LeMaoult, Jose A. Guevara-Patino, Beatrix M. Metzner, Janko Nikolich-Žugich

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

Peripheral T cell diversity is virtually constant in the young, but is invariably reduced in aged mice and humans. CD8+ T cell clonal expansions (TCE) are the most drastic manifestation of, and possible contributors to, this reduced diversity. We show that the presence of TCE results in reduced CD8+, but not CD4+, T cell diversity, and in functional inability to mobilize parts of the CD8+ T cell repertoire affected by TCE. In the model of herpes simplex virus (HSV)-1 infection of B6 mice, >90% of the responding CD8+ T cells use Vβ10 or Vβ8 and are directed against a single glycoprotein B (gB 498-505) epitope, gB-8p. We found that old animals bearing CD8 + TCE within Vβ10 or Vβ8 families failed to mount an effective immune response against HSV-1, as judged by reduced numbers of peptide-major histocompatibility complex tetramer+ CD8 T cells and an absence of antiviral lytic function. Furthermore, Vβ8 TCE experimentally introduced into young mice resulted in lower resistance to viral challenge, whereas Vβ5+ TCE induced in a similar fashion did not impact viral resistance. These results demonstrate that age-related TCE functionally impair the efficacy of antiviral CD8+ T cell immunity in an antigen-specific manner, strongly suggesting that TCE are not the mere manifestation of, but are also a contributing factor to, the immunodeficiency of senescence.

Original languageEnglish (US)
Pages (from-to)1347-1358
Number of pages12
JournalJournal of Experimental Medicine
Volume200
Issue number10
DOIs
StatePublished - Nov 15 2004
Externally publishedYes

Keywords

  • Aging
  • Antiviral immunity
  • Repertoire diversity
  • T cell clonal expansions
  • TCR

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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