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

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

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66 Citations (Scopus)

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
DOIs
Publication statusPublished - 2 May 2018
Externally publishedYes

Keywords

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

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