Eomesodermin promotes the development of type 1 regulatory T (TR1) cells

Type 1 regulatory T (T(R)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 T(R)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 T(R)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 T(R)1 cells requires T-bet and donor macrophage-derived IL-27. Thus, we define the cellular and transcriptional control of T(R)1 cell differentiation during BMT, opening new avenues to therapeutic manipulation.