High CD26 and Low CD94 Expression Identifies an IL-23 Responsive V delta 2(+) T Cell Subset with a MAIT Cell-like Transcriptional Profile
AuthorWragg, KM; Tan, H-X; Kristensen, AB; Nguyen-Robertson, C; Kelleher, AD; Parsons, MS; Wheatley, AK; Berzins, SP; Pellicci, DG; Kent, SJ; ...
Source TitleCell Reports
University of Melbourne Author/sWheatley, Adam; Kent, Stephen; Pellicci, Daniel; Berzins, Stuart; Nguyen-Robertson, Catriona; Juno, Jennifer; Wragg, Kathleen; Parsons, Matt; Kristensen, Anne; Tan, Hyon Xhi
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsWragg, K. M., Tan, H. -X., Kristensen, A. B., Nguyen-Robertson, C., Kelleher, A. D., Parsons, M. S., Wheatley, A. K., Berzins, S. P., Pellicci, D. G., Kent, S. J. & Juno, J. A. (2020). High CD26 and Low CD94 Expression Identifies an IL-23 Responsive V delta 2(+) T Cell Subset with a MAIT Cell-like Transcriptional Profile. CELL REPORTS, 31 (11), https://doi.org/10.1016/j.celrep.2020.107773.
Access StatusOpen Access
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.
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