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

MS Davey, CR Willcox, S Hunter… - Nature …, 2018 - nature.com
Nature communications, 2018nature.com
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 …
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.
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