Mapping of γ/δ t cells reveals vδ2+ t cells resistance to senescence

• Main Authors: Xu, Weili, Monaco, Gianni, Wong, Eleanor Huijin, Tan, Wilson Lek Wen, Kared, Hassen, Simoni, Yannick, Tan, Shu Wen, How, Wilson Zhi Yong, Tan, Crystal Tze Ying, Lee, Bernett Teck Kwong, Carbajo, Daniel, K.G., Srinivasan, Low, Ivy Chay Huang, Mok, Esther Wing Hei, Foo, Shihui, Lum, Josephine, Tey, Hong Liang, Tan, Wee Ping, Poidinger, Michael, Newell, Evan, Ng, Tze Pin, Foo, Roger, Akbar, Arne N., Fülöp, Tamas, Larbi, Anis
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2019
• Subjects: Cellular Senescence; Aging; DRNTU::Science::Biological sciences::Microbiology::Immunology
• Online Access: https://hdl.handle.net/10356/89850; http://hdl.handle.net/10220/47744
• Institution: Nanyang Technological University

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 characterise 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 “adaptivelike” Vδ1+ T cells.