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

Tissue-resident memory T (T-RM) cells provide rapid front-line protection against infection. Veldhoen and colleagues demonstrate that the type 1 regulatory T cell subset supports generation of T-RM 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-beta 8 endows the bioavailability of transforming growth factor-beta in the microenvironment, thereby promoting the generation of CD8(+) T-RM cells.