High CD26 and Low CD94 Expression Identifies an IL-23 Responsive Vδ2+ T Cell Subset with a MAIT Cell-like Transcriptional Profile

Kathleen M. Wragg; Hyon-Xhi Tan; Anne B. Kristensen; Catriona V. Nguyen-Robertson; Anthony D. Kelleher; Matthew S. Parsons; Adam K. Wheatley; Stuart P. Berzins; Daniel G. Pellicci; Stephen J. Kent; Jennifer A. Juno

Cell Reports (Jun 2020)

High CD26 and Low CD94 Expression Identifies an IL-23 Responsive Vδ2+ T Cell Subset with a MAIT Cell-like Transcriptional Profile

Kathleen M. Wragg,
Hyon-Xhi Tan,
Anne B. Kristensen,
Catriona V. Nguyen-Robertson,
Anthony D. Kelleher,
Matthew S. Parsons,
Adam K. Wheatley,
Stuart P. Berzins,
Daniel G. Pellicci,
Stephen J. Kent,
Jennifer A. Juno

Affiliations

Kathleen M. Wragg: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia
Hyon-Xhi Tan: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia
Anne B. Kristensen: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia
Catriona V. Nguyen-Robertson: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, VIC 3000, Australia
Anthony D. Kelleher: The Kirby Institute, University of New South Wales, Kensington, NSW 2052, Australia; St. Vincent’s Centre for Applied Medical Research, St. Vincent’s Hospital, Darlinghurst, NSW 2011, Australia
Matthew S. Parsons: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Division of Microbiology and Immunology, Yerkes National Primate Research Center, Atlanta, GA 30329, USA; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA
Adam K. Wheatley: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia
Stuart P. Berzins: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Federation University and Fiona Elsey Cancer Research Institute, Ballarat, VIC 3350, Australia
Daniel G. Pellicci: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia
Stephen J. Kent: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Carlton, VIC 3053, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3000, Australia; Corresponding author
Jennifer A. Juno: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia; Corresponding author

Journal volume & issue: Vol. 31, no. 11
p. 107773

Abstract

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Summary: Vδ2+ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2+ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2+ cells exhibit substantial similarities to CD26hi mucosal-associated invariant T (MAIT) cells, although CD26− Vδ2+ cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2+Vγ9+ population is dominated by CD26hiCD94lo cells; during adolescence and adulthood, Vδ2+ cells acquire CD94/NKG2A expression and the relative frequency of the CD26hiCD94lo subset declines. Critically, exposure of the CD26hiCD94lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26hiCD94lo Vδ2+ cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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