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

T cell receptor (TCR) Vγ4 + expressing γ δ T cells can be divided into IFN-γ and IL-17-producing effector T cell subsets. A bias towards γ δ 17 effector fate decisions is observed during early ontogeny. In contrast, the existence of Vγ4 + γ δ 17 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 γ δ 17 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 γ δ 17-like cells from adult thymus lack transcriptional activity of the Scart2 encoding gene, suggesting that Scart2 is a distinct trait of fetal γ δ 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 γ δ 17-like cells within the adult thymus. Highlights Transcriptional and epigenetic profiling identifies developmental plasticity of Gzma + Cd24a + Vγ4 cells in adult thymus. Thymic c-Maf + and RORγt + Vγ4 T cells can be generated during adulthood, but do not reach the periphery under steady-state conditions. Innate CD44 high CD45RB neg γ δ 17 cells are completely absent upon induction of T cell development during adulthood. Scart2 expression might be a key molecule to track developmental traits of fetal-derived γ δ 17 cell precursors.