Type 1 T reg cells promote the generation of CD8 + tissue-resident memory T cells.

Tissue-resident memory T (T _RM ) cells, functionally distinct from circulating memory T cells, have a critical role in protective immunity in tissues, are more efficacious when elicited after vaccination and yield more effective antitumor immunity, yet the signals that direct development of T _RM cells are incompletely understood. Here we show that type 1 regulatory T (T _reg ) cells, which express the transcription factor T-bet, promote the generation of CD8 ⁺ T _RM cells. The absence of T-bet-expressing type 1 T _reg cells reduces the presence of T _RM cells in multiple tissues and increases pathogen burden upon infectious challenge. Using infection models, we show that type 1 T _reg cells are specifically recruited to local inflammatory sites via the chemokine receptor CXCR3. Close proximity with effector CD8 ⁺ T cells and T _reg cell expression of integrin-β8 endows the bioavailability of transforming growth factor-β in the microenvironment, thereby promoting the generation of CD8 ⁺ T _RM cells.