title: Defective T Memory Cell Differentiation after Varicella Zoster Vaccination in Older Individuals.
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.
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States of America.|Department of Medicine, VAPAHCS, Palo Alto, California, United States of America.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States of America.|Department of Medicine, VAPAHCS, Palo Alto, California, United States of America.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Cavanagh
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States of America.|Department of Medicine, VAPAHCS, Palo Alto, California, United States of America.
authors.forename: Sabine
authors.identifier: http://orcid.org/0000-0002-3125-7242
authors.initials: S
authors.lastname: Le Saux
authors.affiliation: Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, United States of America.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Wagar
authors.affiliation: Department of Pediatrics-Infectious Diseases, Stanford University, Stanford, California, United States of America.
authors.forename: Sally
authors.initials: S
authors.lastname: Mackey
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States of America.|Department of Medicine, VAPAHCS, Palo Alto, California, United States of America.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, United States of America.
authors.forename: Holden
authors.initials: H
authors.lastname: Maecker
authors.affiliation: Department of Medicine, Stanford Prevention Research Center, Stanford University, Stanford, California, United States of America.
authors.forename: Gary E
authors.identifier: http://orcid.org/0000-0001-5583-9629
authors.initials: GE
authors.lastname: Swan
authors.affiliation: Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, California, United States of America.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Department of Pediatrics-Infectious Diseases, Stanford University, Stanford, California, United States of America.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Department of Biomedical Data Science, Stanford University, Stanford, California, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States of America.|Department of Medicine, VAPAHCS, Palo Alto, California, United States of America.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Weyand
authors.affiliation: Department of Medicine, Division of Immunology and Rheumatology, Stanford University, Stanford, California, United States of America.|Department of Medicine, VAPAHCS, Palo Alto, California, United States of America.
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Goronzy
mesh_terms: D000368:Aged; D002454:Cell Differentiation / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006562:Herpes Zoster / Q000276:immunology* / Q000517:prevention & control; D053061:Herpes Zoster Vaccine / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D053061:Herpes Zoster Vaccine