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

Cell Rep. 2020 Jun 16;31(11):107773. doi: 10.1016/j.celrep.2020.107773.


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.

Keywords: CD26; CD94; IL-23; MAIT; Vd2; Vg9; gamma delta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dipeptidyl Peptidase 4 / metabolism*
  • Humans
  • Interleukin-23 / metabolism*
  • Lymphocyte Activation / immunology
  • NK Cell Lectin-Like Receptor Subfamily D / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • T-Lymphocyte Subsets / metabolism*


  • Interleukin-23
  • KLRD1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily D
  • Receptors, Antigen, T-Cell, gamma-delta
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4