INSERM U1163 and CNRS ERL 8254, Faculté de Médecine, Université Paris Descartes, Hôpital Necker, 75015 Paris, France. Faculté de Médecine and Université Paris-Sud, 94805 Villejuif, France. Institut Hospitalo-Universitaire Imagine, Université Sorbonne Paris Cité, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, 75015 Paris, France.
Institute of Immunity and Transplantation, University College London, London NW3 2PF, UK. Cancer Institute, University College London, London WC1E 6DD, UK.
Sci Transl Med. 2015 Apr 1;7(281):281ra42. doi: 10.1126/scitranslmed.3010435.
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.
粒细胞集落刺激因子 (G-CSF) 通常用于从健康供体中采集外周血干细胞 (PBSC)，用于异基因造血干细胞移植 (allo-HSCT)。我们表明，在人类和小鼠中，G-CSF 动员具有成熟单核细胞特征的 CD34(+) 细胞亚群。这些细胞在小鼠和人类中具有表型和功能上的一致性，与髓样和单核细胞前体不同，但与成熟单核细胞相似，并具有免疫抑制特性。这些细胞对活化 T 细胞释放的干扰素-γ作出反应，产生一氧化氮，从而在体外和体内诱导同种异体 T 细胞死亡。凋亡的 T 细胞被巨噬细胞吞噬，巨噬细胞释放转化生长因子-β并促进调节性 T 细胞扩增。事实上，外周血 CD34(+) 细胞中 CD34(+) 单核细胞的比例与人类急性移植物抗宿主病 (GVHD) 的发生率呈负相关。因此，G-CSF 动员的细胞是一种有吸引力的候选群体，可以在体外扩增用于对抗 GVHD 的细胞治疗。
