Partial Compensation of IL-17 Production by Vγ1 T Cells in the Absence of Vγ4 and Vγ6 T Cells

Abstract

γδ T cells are unconventional T cells that group into different subsets based on the usage of variable γδ T cell receptor (TCR) gene segments, body location, and functionality. γδ T cells that secrete the proinflammatory cytokine interleukin 17 (IL-17) predominantly express a Vγ4⁺ or Vγ6⁺ γδ TCR. The biology and the importance of the γδ TCR of IL-17-producing γδ T cells are not well understood. Here, we investigated the IL-17 production capability of γδ T cells in mice deficient for Vγ4⁺ and Vγ6⁺ γδ TCRs using flow cytometry, TCR-seq, and single-cell transcriptomics. Our data show that Vγ1 T cells only partially compensate for the loss of IL-17⁺ Vγ4 and Vγ6 T cell subsets in lymphoid and nonlymphoid tissues. They develop pre- and postnatally and were predominantly detectable in their physiological body habitats. Collectively, the data underscore the nonredundant roles of Vγ4⁺ and Vγ6⁺ subsets in IL-17-mediated immunity.