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

Several subsets of Foxp3(+) regulatory T cells (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-gamma, Foxp3(+) T-reg cells upregulated the T helper type 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 cell-mediated inflammation. Furthermore, T-bet expression was required for the homeostasis and function of T-reg cells during type 1 inflammation. Thus, in a subset of CD4(+) T cells, the activities of the transcription factors Foxp3 and T-bet are overlaid, which results in T-reg cells with unique homeostatic and migratory properties optimized for the suppression of T(H)1 responses in vivo.