Mapping of γ/δ T cells Reveals Vδ2 T cells Resistance to Senescence

Studies in human aging mainly focus on αβ T cells while γδ T cells have been neglected despite their role in immunosurveillance. In this study, we investigated γδ T cells and its subsets (i.e. Vδ1 , Vδ2 and DN γδ (γδ Vδ1-Vδ2-)) by deep immunophenotyping. Our data shows that peripheral Vδ2 are differentially susceptible to life-long stresses against all other αβ and γδ T cells. Using aging and cytomegalovirus history (the main confounding factor in immune-aging studies) as immunological models and via functional assays, telomere length determination, epigenetic methylome profiling and DNA damage response capacity, we show that Vδ2 T cells are resistant from cellular senescence. Our results highlight the differential impact of stress on γδ T cells subsets, reveal surface markers that are functionally relevant for γδ T cells subsets and highlight possible mechanisms that enable Vδ2 to be resistant to cellular aging. This new finding reinforces the concept that Vδ2 have an “innate-like” behavior and are more resilient to the environment as compared to “adaptive-like” Vδ1 T cells. Funding Statement: Weili Xu is funded by A*STAR Graduate Academy (AGA). The work was funded by the Singapore Immunology Network, the Agency for Science Technology and Research (JCO grant #1434m00115) and the Skin Research Institute of Singapore (SRG grant #14018). Declaration of Interests: The authors have no conflict of interests. Ethics Approval Statement: Participants of the study were recruited under National University of Singapore Institutional Review Board (IRB code NUS-IRB 01-256). Cone blood was obtained from Health Science Authority (HSA) Singapore, approved under NUS-IRB 10-250.