Adult thymus-derived cMaf⁺RORγt⁺γδ T cells lack Scart2 chromatin accessibility and do not reach periphery

Abstract

T cell receptor (TCR) Vγ4+ expressing γδ T cells can be divided into IFN-γ and IL-17-producing effector T cell subsets. A bias towards γδ17 effector fate decisions is observed during early ontogeny. In contrast, the existence of Vγ4+ γδ17 cells derived from adult thymus is still controversial. In the present work, we used a mouse model where T cells are exclusive generated within an adult thymus. Additionally, we employed single-cell chromatin state analysis from thymocytes of normal mice. A small, but considerable population of immature Cd24+ Gzma+ Vγ4 cells was found that exhibit molecular programs of γδ17 cells. These adult thymus-derived immature Cd24a+ cMaf+ Vγ4 cells secrete small amounts of IL-17A and IL-17F. Interestingly, do not reach the periphery under steady-state conditions. Furthermore, de novo generated γδ17-like cells from adult thymus lack transcriptional activity of the Scart2 encoding gene, suggesting that Scart2 is a distinct trait of fetal γδ T cell precursors. Together, this study provides valuable insights into developmental traits of Vγ4 cells during adulthood and raises the question on signals suppressing the full maturation and/or thymic export of γδ17-like cells within the adult thymus.