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

Autor: 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
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: PLoS Pathogens, Vol 12, Iss 10, p e1005892 (2016)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1005892
Popis: 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.
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