Sci Transl Med 2015 Apr;7(281):281ra42
INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France. Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France. INSERM UMRs 938, Centre de recherche de l'hôpital Saint Antoine, 75012 Paris, France. Université Pierre et Marie Curie, Paris VI, 75006 Paris, France.
Granulocyte colony-stimulating factor (G-CSF) is routinely used to collect peripheral blood stem cells (PBSCs) from healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). We show that, in both humans and mice, G-CSF mobilizes a subset of CD34(+) cells with mature monocyte features. These cells, which are phenotypically and functionally conserved in mice and humans, are transcriptionally distinct from myeloid and monocytic precursors but similar to mature monocytes and endowed with immunosuppressive properties. In response to interferon-γ released by activated T cells, these cells produce nitric oxide, which induces allogeneic T cell death both in vitro and in vivo. These apoptotic T cells are engulfed by macrophages that release transforming growth factor-β and promote regulatory T cell expansion. Indeed, the fraction of CD34(+) monocytes in peripheral blood CD34(+) cells inversely correlates with the incidence of acute graft-versus-host disease (GVHD) in humans. Therefore, G-CSF-mobilized cells are an attractive candidate population to be expanded ex vivo for cellular therapy against GVHD.