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

Background: Immune adaptation with aging is a major of health outcomes. Studies in humans have mainly focus on alpha beta T cells while gamma delta T cells have been neglected despite their role in immunosurveillance. We investigated the impact of aging on gamma delta 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 gamma d 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 gamma d T cell subsets phenotype. Findings: Our data shows that peripheral V delta 2+ phenotype, functional capacity (cytokines, cytotoxicity, proliferation) and gene expression profile are specific when compared against all other alpha beta and gamma delta T cells in aging. Hallmarks of senescence including telomere length, epigenetic profile and DNA damage response of V delta 2+ also differs against all other alpha beta and gamma delta T cells. Interpretation: Our results highlight the differential impact of lifelong stress on V delta T cells subsets, and highlight possible mechanisms that enable V delta 2+ to be resistant to cellular aging. The new findings reinforce the concept that V delta 2+ have an innate-like behavior and are more resilient to the environment as compared to adaptivelike V delta 1+ T cells. (c) 2018 The Authors. Published by Elsevier B.V.