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

Cell Reports

Anthony D. Kelleher¹  Stephen J. Kent²  Daniel G. Pellicci³  Adam K. Wheatley⁴  Jennifer A. Juno⁵  Stuart P. Berzins⁵  Anne B. Kristensen⁵  Catriona V. Nguyen-Robertson⁵  Hyon-Xhi Tan⁵  Kathleen M. Wragg⁵  Matthew S. Parsons⁶ 

[1] ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, VIC 3000, Australia;Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA;Division of Microbiology and Immunology, Yerkes National Primate Research Center, Atlanta, GA 30329, USA;St. Vincent’s Centre for Applied Medical Research, St. Vincent’s Hospital, Darlinghurst, NSW 2011, Australia;Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3000, Australia;The Kirby Institute, University of New South Wales, Kensington, NSW 2052, Australia;

关键词: gamma delta;    CD26;    Vd2;    CD94;    MAIT;    Vg9;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown