Eomesodermin promotes the development of type 1 regulatory T (T R 1) cells.

Type 1 regulatory T (TR 1) cells are Foxp3- interleukin-10 (IL-10)-producing CD4+ T cells with potent immunosuppressive properties, but their requirements for lineage development have remained elusive. We show that TR 1 cells constitute the most abundant regulatory population after allogeneic bone marrow transplantation (BMT), express the transcription factor Eomesodermin (Eomes), and are critical for the prevention of graft-versus-host disease. We demonstrate that Eomes is required for TR 1 cell differentiation, during which it acts in concert with the transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) by transcriptionally activating IL-10 expression and repressing differentiation into other T helper cell lineages. We further show that Eomes induction in TR 1 cells requires T-bet and donor macrophage-derived IL-27. Thus, we define the cellular and transcriptional control of TR 1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.