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
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.
