We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Human γδ T‐cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation.
- Authors
Sant, Sneha; Jenkins, Misty R; Dash, Pradyot; Watson, Katherine A; Wang, Zhongfang; Pizzolla, Angela; Koutsakos, Marios; Nguyen, Thi HO; Lappas, Martha; Crowe, Jane; Loudovaris, Tom; Mannering, Stuart I; Westall, Glen P; Kotsimbos, Tom C; Cheng, Allen C; Wakim, Linda; Doherty, Peter C; Thomas, Paul G; Loh, Liyen; Kedzierska, Katherine
- 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‐cell RT‐PCR, we characterised paired TCRγδ clonotypes for influenza‐reactive γδ T cells in comparison with TCRs from healthy neonates, adults, elderly donors and tissues. Results: We provide the first visual evidence of γδ T‐cell‐mediated killing of influenza‐infected targets and show distinct features to those reported for CD8+ T cells. γδ T cells displayed poly‐cytotoxic profiles in influenza‐infected patients and produced IFN‐γ towards influenza‐infected cells. These IFN‐γ‐producing γδ T cells were skewed towards the γ9δ2 TCRs, particularly expressing the public GV9‐TCRγ, capable of pairing with numerous TCR‐δ chains, suggesting their significant role in γδ T‐cell immunity. Neonatal γδ T cells displayed extensive non‐overlapping TCRγδ repertoires, while adults had enriched γ9δ2‐pairings with diverse CDR3γδ regions. Conversely, the elderly showed distinct γδ‐pairings characterised by large clonal expansions, a profile also prominent in adult tissues. Conclusion: Human TCRγδ repertoire is shaped by age, tissue compartmentalisation and the individual's history of infection, suggesting that these somewhat enigmatic γδ T cells indeed respond to antigen challenge.
- Subjects
INFLUENZA viruses; T cells; VIDEO microscopy; EPITHELIAL cells; BLOOD cells
- Publication
Clinical & Translational Immunology, 2019, Vol 8, Issue 9, pN.PAG
- ISSN
2050-0068
- Publication type
Article
- DOI
10.1002/cti2.1079