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

Martin Davey, Carrie Willcox, Stuart Hunter, Sofya A. Kasatskaya, Ester B.M. Remmerswaal, Mahboob Salim, Fiyaz Mohammed, Frederike J. Bemelman, Dmitriy M. Chudakov, Ye Htun Oo, Benjamin Willcox

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70 Citations (Scopus)
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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.

Original languageEnglish
Article number1760
Number of pages14
JournalNature Communications
Volume9
Issue number1
Early online date2 May 2018
DOIs
Publication statusPublished - Dec 2018

Keywords

  • clonal selection
  • next-generation sequencing
  • T-cell receptor
  • viral infection

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