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

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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. Wragg et al. identify a population of human gd T cells with striking similarities to MAIT cells. These cells dominate the cord blood Vd2 population and upregulate an effector-like program upon antigen and IL-23 stimulation, providing a potential mechanism by which cytotoxic Vd2 cells may accumulate during adolescence and adulthood.

Original languageEnglish
Article number107773
Number of pages24
JournalCell Reports
Issue number11
Publication statusPublished - 16 Jun 2020


  • CD26
  • CD94
  • gamma delta
  • IL-23
  • MAIT
  • Vd2
  • Vg9

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