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

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

Author(s): Sant, S; Jenkins, MR; Dash, P; Watson, KA; Wang, Z; Pizzolla, A; Koutsakos, M; Nguyen, TH; Lappas, M; Crowe, J; Loudovaris, T; Mannering, SI; Westall, GP; Kotsimbos, TC; Cheng, AC; Wakim, L; Doherty, PC; Thomas, PG; Loh, L; Kedzierska, K;
Details: Publication Year 2019,Volume 8,Issue #9,Page e1079
Journal Title: Clinical & Translational Immunology
Publication Type: Journal Article
Abstract: Background: Although gammadelta 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 gammadelta T cells towards influenza viruses and defined influenza-reactive gammadelta TCRs in the context of gammadelta-TCRs across the human lifespan. Methods: We performed (51)Cr-killing assay and single-cell time-lapse live video microscopy to define mechanisms underlying gammadelta T-cell-mediated killing of influenza-infected targets. We assessed cytotoxic profiles of gammadelta T cells in influenza-infected patients and IFN-gamma production towards influenza-infected lung epithelial cells. Using single-cell RT-PCR, we characterised paired TCRgammadelta clonotypes for influenza-reactive gammadelta T cells in comparison with TCRs from healthy neonates, adults, elderly donors and tissues. Results: We provide the first visual evidence of gammadelta T-cell-mediated killing of influenza-infected targets and show distinct features to those reported for CD8(+) T cells. gammadelta T cells displayed poly-cytotoxic profiles in influenza-infected patients and produced IFN-gamma towards influenza-infected cells. These IFN-gamma-producing gammadelta T cells were skewed towards the gamma9delta2 TCRs, particularly expressing the public GV9-TCRgamma, capable of pairing with numerous TCR-delta chains, suggesting their significant role in gammadelta T-cell immunity. Neonatal gammadelta T cells displayed extensive non-overlapping TCRgammadelta repertoires, while adults had enriched gamma9delta2-pairings with diverse CDR3gammadelta regions. Conversely, the elderly showed distinct gammadelta-pairings characterised by large clonal expansions, a profile also prominent in adult tissues. Conclusion: Human TCRgammadelta repertoire is shaped by age, tissue compartmentalisation and the individual's history of infection, suggesting that these somewhat enigmatic gammadelta T cells indeed respond to antigen challenge.
Publisher: Wiley
Research Division(s): Immunology
PubMed ID: 31559018
Publisher's Version: https://doi.org/10.1002/cti2.1079
Open Access at Publisher's Site: https://doi.org/10.1002/cti2.1079
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2019-10-23 02:22:54

Last Modified: 2019-10-23 02:47:38