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

65 Pages Posted: 18 Oct 2018

See all articles by Weili Xu

Weili Xu

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Gianni Monaco

University of Basel - Department of Biomedicine

Eleanor Huijin Wong

Agency for Science, Technology and Research (A*STAR)

Wilson Lek Wen Tan

Agency for Science, Technology and Research (A*STAR)

Hassen Kared

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Yannick Simoni

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Shu Wen Tan

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Wilson Zhi Yong How

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Crystal Tze Ying Tan

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Bernett Lee

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Daniel Carbajo

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Srinivasan K.G.

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Ivy Chay Huang Low

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Esther Wing Hei Mok

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Shihui Foo

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Josephine Lum

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Hong Liang Tey

National Skin Center Singapore

Wee Ping Tan

National Skin Center Singapore

Michael Poidinger

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Evan Newell

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

Tze Pin Ng

National University of Singapore (NUS)

Roger Foo

Agency for Science, Technology and Research (A*STAR)

Arne N. Akbar

University College London

Tamas Fülöp

Université de Sherbrooke

Anis Larbi

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

More...

Abstract

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.

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

Suggested Citation

Xu, Weili and Monaco, Gianni and Wong, Eleanor Huijin and Tan, Wilson Lek Wen and Kared, Hassen and Simoni, Yannick and Tan, Shu Wen and How, Wilson Zhi Yong and Tan, Crystal Tze Ying and Lee, Bernett and Carbajo, Daniel and K.G., Srinivasan and Low, Ivy Chay Huang and Mok, Esther Wing Hei and Foo, Shihui and Lum, Josephine and Tey, Hong Liang and Tan, Wee Ping and Poidinger, Michael and Newell, Evan and Ng, Tze Pin and Foo, Roger and Akbar, Arne N. and Fülöp, Tamas and Larbi, Anis, Mapping of γ/δ T cells Reveals Vδ2 T cells Resistance to Senescence (October 14, 2018). Available at SSRN: https://ssrn.com/abstract=3266976 or http://dx.doi.org/10.2139/ssrn.3266976

Weili Xu (Contact Author)

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Gianni Monaco

University of Basel - Department of Biomedicine ( email )

Petersplatz 1
Basel, CH-4003
Switzerland

Eleanor Huijin Wong

Agency for Science, Technology and Research (A*STAR)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Wilson Lek Wen Tan

Agency for Science, Technology and Research (A*STAR)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Hassen Kared

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Yannick Simoni

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Shu Wen Tan

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Wilson Zhi Yong How

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Crystal Tze Ying Tan

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Bernett Lee

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN) ( email )

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Daniel Carbajo

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Srinivasan K.G.

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Ivy Chay Huang Low

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Esther Wing Hei Mok

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Shihui Foo

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Josephine Lum

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Hong Liang Tey

National Skin Center Singapore

Singapore

Wee Ping Tan

National Skin Center Singapore

Singapore

Michael Poidinger

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Evan Newell

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Tze Pin Ng

National University of Singapore (NUS)

1E Kent Ridge Road
NUHS Tower Block Level 7
Singapore, 119228
Singapore

Roger Foo

Agency for Science, Technology and Research (A*STAR)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

Arne N. Akbar

University College London

Gower Street
London, WC1E 6BT
United Kingdom

Tamas Fülöp

Université de Sherbrooke

2500 bd de l'Universite
Sherbrooke, Québec J1K 2R1
Canada

Anis Larbi

Agency for Science, Technology and Research (A*STAR) - Singapore Immunology Network (SIgN)

1 Fusionopolis Way
#16-16 Connexis
Singapore, 138632
Singapore

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