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

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 CD27(hi)CCR7(+)CD28(+)IL-7Rα(+) naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27(lo)CD45RA(+)CX(3)CR1(+)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.