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

PLoS Pathogens

Mark M. Davis¹  Sabine Le Saux¹  Qian Qi¹  Sally Mackey¹  Cornelia M. Weyand²  Lisa E. Wagar³  Mary M. Cavanagh³  Cornelia L. Dekker³  Jinyu Hu³  Gary E. Swan⁴  Jörg J. Goronzy⁵  Holden Maecker⁵  Lu Tian⁵ 

[1] Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States of America;Department of Medicine, Stanford Prevention Research Center, Stanford University, Stanford, California, United States of America;Department of Medicine, VAPAHCS, Palo Alto, California, United States of America;Department of Pediatrics-Infectious Diseases, Stanford University, Stanford, California, United States of America;Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, United States of America

关键词: T cells;    Vaccination;    immunization;    Gene expression;    Memory T cells;    Vaccines;    Antibodies;    Enzyme-linked immunoassays;    T helper cells;   

DOI  :  10.1371/journal.ppat.1005892

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY