Defective T Memory Cell Differentiation after Varicella Zoster Vaccination in Older Individuals

Qian Qi, Mary M. Cavanagh, Sabine Le Saux, Lisa E. Wagar, Sally Mackey, Jinyu Hu, Holden Maecker, Gary E. Swan, Mark M. Davis, Cornelia L. Dekker, Lu Tian, Cornelia M. Weyand, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Vaccination with attenuated live varicella zoster virus (VZV) can prevent zoster reactivation, but protection is incomplete especially in an older population. To decipher the molecular mechanisms underlying variable vaccine responses, T- and B-cell responses to VZV vaccination were examined in individuals of different ages including identical twin pairs. Contrary to the induction of VZV-specific antibodies, antigen-specific T cell responses were significantly influenced by inherited factors. Diminished generation of long-lived memory T cells in older individuals was mainly caused by increased T cell loss after the peak response while the expansion of antigen-specific T cells was not affected by age. Gene expression in activated CD4 T cells at the time of the peak response identified gene modules related to cell cycle regulation and DNA repair that correlated with the contraction phase of the T cell response and consequently the generation of long-lived memory cells. These data identify cell cycle regulatory mechanisms as targets to reduce T cell attrition in a vaccine response and to improve the generation of antigen-specific T cell memory, in particular in an older population.

Original languageEnglish (US)
Article numbere1005892
JournalPLoS pathogens
Volume12
Issue number10
DOIs
StatePublished - Oct 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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