The Characterization of Varicella Zoster Virus-Specific T Cells in Skin and Blood during Aging

J Invest Dermatol. 2015 Jul;135(7):1752-1762. doi: 10.1038/jid.2015.63. Epub 2015 Mar 3.


Reactivation of the varicella zoster virus (VZV) increases during aging. Although the effects of VZV reactivation are observed in the skin (shingles), the number and functional capacity of cutaneous VZV-specific T cells have not been investigated. The numbers of circulating IFN-γ-secreting VZV-specific CD4(+) T cells are significantly decreased in old subjects. However, other measures of VZV-specific CD4(+) T cells, including proliferative capacity to VZV antigen stimulation and identification of VZV-specific CD4(+) T cells with an major histocompatibility complex class II tetramer (epitope of IE-63 protein), were similar in both age groups. The majority of T cells in the skin of both age groups expressed CD69, a characteristic of skin-resident T cells. VZV-specific CD4(+) T cells were significantly increased in the skin compared with the blood in young and old subjects, and their function was similar in both age groups. In contrast, the number of Foxp3(+) regulatory T cells and expression of the inhibitory receptor programmed cell death -1 PD-1 on CD4(+) T cells were significantly increased in the skin of older humans. Therefore, VZV-specific CD4(+) T cells in the skin of older individuals are functionally competent. However, their activity may be restricted by multiple inhibitory influences in situ.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Aging / physiology
  • Biopsy, Needle
  • CD4-Positive T-Lymphocytes / immunology*
  • Case-Control Studies
  • Cells, Cultured
  • Cohort Studies
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Herpes Zoster / epidemiology
  • Herpes Zoster / physiopathology
  • Herpesvirus 3, Human / immunology*
  • Herpesvirus 3, Human / pathogenicity
  • Humans
  • Immunologic Memory
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / virology
  • Male
  • Middle Aged
  • Reference Values
  • Skin / immunology
  • Skin / pathology
  • Statistics, Nonparametric
  • T-Lymphocytes, Regulatory / immunology*
  • Virus Activation / immunology*
  • Young Adult