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
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..View full abstract
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Awarded by Australian National Health and Medical Research Council (NHMRC)
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).