Journal article

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

Sneha Sant, Misty R Jenkins, Pradyot Dash, Katherine A Watson, Zhongfang Wang, Angela Pizzolla, Marios Koutsakos, Thi HO Nguyen, Martha Lappas, Jane Crowe, Tom Loudovaris, Stuart Mannering, Glen P Westall, Tom C Kotsimbos, Allen C Cheng, Linda Wakim, Peter C Doherty, Paul G Thomas, Liyen Loh, Katherine Kedzierska

CLINICAL & TRANSLATIONAL IMMUNOLOGY | WILEY | Published : 2019

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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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


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).