RORγt+ c-Maf+Vγ4+ γδ T cells are generated in the adult thymus but do not reach the periphery

T cell receptor (TCR) Vy4-expressing y8 T cells comprise interferon y (IFNy)-and interleukin-17 (IL-17) producing effector subsets, with a preference for IL-17 effector fate decisions during early ontogeny. The existence of adult-thymus-derived IL-17+ T cells (y817) remains controversial. Here, we use a mouse model in which T cells are generated exclusively in the adult thymus and employ single-cell chromatin state analysis to study their development. We identify adult-thymus-derived Vy4 T cells that have all the molecular programs to become IL-17 producers. However, they have reduced IL-17 production capabilities and rarely reach the periphery. Moreover, this study provides high-resolution profiles of Vy4 T cells in the adult thymus and lymph nodes and identifies Zeb1 as a potential y817 cell regulator. Together, this study provides valuable insights into the developmental traits of Vy4 T cells during adulthood and supports the idea of age-specific signals required for thymic export and/or peripheral maturation of y817 cells.

Automated summary

This study investigates the development of Vy4 T cells in the adult thymus using a mouse model and single-cell chromatin state analysis. The results reveal that the adult-thymus-derived Vy4 T cells have the molecular programs to become IL-17 producers, but their IL-17 production capabilities are reduced and they rarely reach the periphery. The study also identifies Zeb1 as a potential regulator of y817 cells.