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Nat Commun. 2018 May 2;9(1):1760. doi: 10.1038/s41467-018-04076-0.

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

Author information

1
Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK. m.davey@bham.ac.uk.
2
Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
3
Centre for Liver Research and NIHR Biomedical Research Unit in Liver Disease, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK.
4
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, 117997, Russia.
5
Centre for Data-Intensive Biomedicine and Biotechnology, Skolkovo Institute of Science and Technology, Moscow, 143026, Russia.
6
Department of Experimental Immunology, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
7
Renal Transplant Unit, Division of Internal Medicine, Academic Medical Center, Amsterdam, 1105 AZ, The Netherlands.
8
Central European Institute of Technology, Masaryk University, Brno, 625 00, Czech Republic.
9
Pirogov Russian National Research Medical University, Moscow, 117997, Russia.
10
Cancer Immunology and Immunotherapy Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK. b.willcox@bham.ac.uk.

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.

PMID:
29720665
PMCID:
PMC5932074
DOI:
10.1038/s41467-018-04076-0
[Indexed for MEDLINE]
Free PMC Article

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