In this issue of Blood, Piper et al find that donor T cells that secrete granulocytemacrophage colony-stimulating factor (GM-CSF) promote graft-versus-host disease (GVHD) by recruiting donor dendritic cells. 1 This amplifies the activation of alloreactive T cells and increases the severity of GVHD. The authors identified GM-CSF secretion in a rare population of CD11c+ CD4+ T cells that express the transcription factor Bhlhe40. Piper et al showed that Bhlhe40+ CD4+ donor T cells are central to the development of GVHD in the gut in murine models of allogeneic bone marrow transplantation (BMT). Transplantation of either GM-CSF or Bhlhe40 knockout donor T cells resulted in significantly lower incidence of GVHD in allogeneic BMT recipients. This paper is of broad interest to hematologists and immunologists as it illuminates the role of donor T cells in activating dendritic cells and positions GM-CSF–producing T cells as a critical link between innate and adaptive immune responses.

The physiological role for GM-CSF has been unclear. GM-CSF was the first colonystimulating factor to enter clinical trials and is Food and Drug Administration approved for treatment of neutropenia after chemotherapy, stem cell transplantation, graft failure, or stem cell mobilization. 2 In clinical practice, the use of GM-CSF in neutropenic patients and stem cell mobilization has largely been supplanted by granulocyte