T-bet controls regulatory T cell homeostasis and function during type-1 inflammation

Several subsets of Foxp3(+) regulatory T (T(reg)) cells work in concert to maintain immune homeostasis. However, the molecular bases underlying the phenotypic and functional diversity of T(reg) cells remain obscure. We show that in response to interferon-γ, Foxp3(+) T(reg) cells upregulated the T helper 1 (T(H)1)-specifying transcription factor T-bet. T-bet promoted expression of the chemokine receptor CXCR3 on T(reg) cells, and T-bet(+) T(reg) cells accumulated at sites of T(H)1-mediated inflammation. Furthermore, T-bet expression was required for the homeostasis and function of T(reg) cells during type-1 inflammation. Thus, within a subset of CD4(+) T cells, the activities of Foxp3 and T-bet are overlaid, resulting in T(reg) cells with unique homeostatic and migratory properties optimized for suppression of T(H)1 responses in vivo.