A new role for an old cytokine: GM-CSF amplifies GVHD

]In this issue of Blood, Piper et al find that donor T cells that secrete granulocyte-macrophage 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.