Mapping of γ/δ T cells reveals Vδ2+ T cells resistance to senescence

EBioMedicine. 2019 Jan:39:44-58. doi: 10.1016/j.ebiom.2018.11.053. Epub 2018 Dec 7.

Abstract

Background: Immune adaptation with aging is a major of health outcomes. Studies in humans have mainly focus on αβ T cells while γδ T cells have been neglected despite their role in immunosurveillance. We investigated the impact of aging on γδ T cell subsets phenotypes, functions, senescence and their molecular response to stress.

Methods: Peripheral blood of young and old donors in Singapore have been used to assess the phenotype, functional capacity, proliferation capacity and gene expression of the various γδ T cell subsets. Peripheral blood mononuclear cells from apheresis cones and young donors have been used to characterize the telomere length, epigenetics profile and DNA damage response of the various γδ T cell subsets phenotype.

Findings: Our data shows that peripheral Vδ2+ phenotype, functional capacity (cytokines, cytotoxicity, proliferation) and gene expression profile are specific when compared against all other αβ and γδ T cells in aging. Hallmarks of senescence including telomere length, epigenetic profile and DNA damage response of Vδ2+ also differs against all other αβ and γδ T cells.

Interpretation: Our results highlight the differential impact of lifelong stress on γδ T cells subsets, and highlight possible mechanisms that enable Vδ2+ to be resistant to cellular aging. The new findings reinforce the concept that Vδ2+ have an "innate-like" behavior and are more resilient to the environment as compared to "adaptive-like" Vδ1+ T cells.

Keywords: Aging; Cellular Senescence; Gamma Delta T cells; Immunobiology; Immunosenescence; Innate Immunity.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / immunology
  • Cell Proliferation
  • Cellular Senescence
  • Cytokines / genetics*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Singapore
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • Telomere Shortening
  • Young Adult

Substances

  • Cytokines
  • Receptors, Antigen, T-Cell, gamma-delta