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 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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