Human γδ T-cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation

S Sant; MR Jenkins; P Dash; KA Watson; Z Wang; A Pizzolla; M Koutsakos; THO Nguyen; M Lappas; J Crowe; T Loudovaris; SI Mannering; GP Westall; TC Kotsimbos; AC Cheng; L Wakim; PC Doherty; PG Thomas; L Loh; K Kedzierska

Journal article

Human γδ T-cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation

S Sant, MR Jenkins, P Dash, KA Watson, Z Wang, A Pizzolla, M Koutsakos, THO Nguyen, M Lappas, J Crowe, T Loudovaris, SI Mannering, GP Westall, TC Kotsimbos, AC Cheng, L Wakim, PC Doherty, PG Thomas, L Loh, K Kedzierska

Clinical and Translational Immunology | WILEY | Published : 2019

DOI: 10.1002/cti2.1079

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Abstract

Background: Although γδ T cells comprise up to 10% of human peripheral blood T cells, questions remain regarding their role in disease states and T-cell receptor (TCR) clonal expansions. We dissected anti-viral functions of human γδ T cells towards influenza viruses and defined influenza-reactive γδ TCRs in the context of γδ-TCRs across the human lifespan. Methods: We performed 51Cr-killing assay and single-cell time-lapse live video microscopy to define mechanisms underlying γδ T-cell-mediated killing of influenza-infected targets. We assessed cytotoxic profiles of γδ T cells in influenza-infected patients and IFN-γ production towards influenza-infected lung epithelial cells. Using single-c..

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University of Melbourne Researchers

Misty Jenkins Author

Angela Pizzolla Author

Marios Koutsakos Author

Oanh Nguyen Author

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Grants

Awarded by National Institute of Allergy and Infectious Diseases

Funding Acknowledgements

We thank ImmunoID facility for FACS sorting and Ms S Gonzalez for technical assistance. The clinical research midwives G Christophers, G Pell, and R Murdoch for sample collection; and the Obstetrics and Midwifery staff of the Mercy Hospital for Women for their co-operation. The Australian National Health and Medical Research Council (NHMRC) NHMRC Program Grant (1071916) to KK supported this work. ML is supported by a Research Fellowship from the Department of Obstetrics and Gynaecology (University of Melbourne) and a Faculty Fellowship from the University of Melbourne. SS was a recipient Victoria India Doctoral Scholarship and Melbourne International Fee Remission Scholarship, University of Melbourne. MK is a recipient of Melbourne International Research Scholarship and Melbourne International Fee Remission Scholarship. MRJ is a NHMRC CDA Research Fellow. KK is a NHMRC Senior Research Level B Fellow (#1102792).