The human Vδ2+ T-cell compartment comprises distinct innate-like Vγ9+ and adaptive Vγ9- subsets

Abstract

Vδ2+ T cells form the predominant human γδ T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-tumour immunity. Here we show that the Vδ2+ compartment comprises both innate-like and adaptive subsets. Vγ9+ Vδ2+ T cells display semi-invariant TCR repertoires, featuring public Vγ9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, Vγ9− Vδ2+ T-cell subset that typically has a CD27hiCCR7+CD28+IL-7Rα+ naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27loCD45RA+CX3CR1+granzymeA/B+ effector phenotype. Consistent with a function in solid tissue immunosurveillance, we detect human intrahepatic Vγ9− Vδ2+ T cells featuring dominant clonal expansions and an effector phenotype. These findings redefine human γδ T-cell subsets by delineating the Vδ2+ T-cell compartment into innate-like (Vγ9+) and adaptive (Vγ9−) subsets, which have distinct functions in microbial immunosurveillance.

γδ T cells in cancer: a small population of lymphocytes with big implications

“…9 On the contrary, IL-17 cd T cells preferentially express CCR6 and the transcription factor PLZF, which is considered to confer innate-like properties to lymphocytes. 20 The Vd2 + subset constitutes an heterogeneous population of cells, producing a range of pro-inflammatory cytokines including IFN-c, IL-17, TNF-a, IL-9, but also IL-10 depending on the setting. [14][15][16] Nevertheless, human thymic cd T cells exhibit de novo expression of type 1 transcription factors T-bet and eomesodermin, reflecting their capacity to rapidly differentiate into cytotoxic effectors producing IFN-c in response to cytokines IL-2 and IL-15.…”

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

“…The dissection of clonality via TCR analysis has, until recently, been limited by our inability to detect paired TCRγδ chains directly ex vivo for single cells. To date, paired analyses have demonstrated signatures of innate‐ and adaptive‐like T cells in the Vδ2 + Vγ9 + and Vδ2 + Vγ9 − , respectively, in human peripheral and umbilical cord blood (CB) . Analysis of TCR repertoire in chronic viral infections within patients suffering CMV reactivation following transplantation has been performed .…”

“…To date, paired analyses have demonstrated signatures of innate-and adaptive-like T cells in the Vd2 + Vc9 + and Vd2 + Vc9 À , respectively, in human peripheral and umbilical cord blood (CB). 14,15 Analysis of TCR repertoire in chronic viral infections within patients suffering CMV reactivation following transplantation has been performed. 14,16 Antigen specificity and clonal expansions from both bulk analyses of c9 + or c9 À T cells, 14,16 and from paired analyses at the single-cell level, were observed, 15 suggesting that there may be specificity for the virus.…”

“…14,15 Analysis of TCR repertoire in chronic viral infections within patients suffering CMV reactivation following transplantation has been performed. 14,16 Antigen specificity and clonal expansions from both bulk analyses of c9 + or c9 À T cells, 14,16 and from paired analyses at the single-cell level, were observed, 15 suggesting that there may be specificity for the virus. It is unknown whether signatures of antigen specificity are apparent in other viral infections, particularly acute infections such as influenza virus.…”

γδ T cells take the stage

“…Studies in mice have highlighted ‘innate‐like’ γδ T cells subsets emerging early in thymic development, bearing semi‐invariant TCRs, suggestive of a limited range of self‐ligands. Recent studies in humans have also identified that a major human γδ T‐cell population, constituting the largest subset of γδ T cells at tissue locations, follow an adaptive immunobiology . In this Special Feature of Clinical & Translational Immunology , we have invited experts in γδ T‐cell biology to provide an overview of the emerging roles of this often overlooked and unique population of T cells in health and disease (Figure ).…”