Introduction: Myeloid-derived suppressor cells (MDSCs) are proposed to control graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the definition of human MDSCs has not yet reached consensus, and the mechanism of MDSCs to control GVHD remains unclear.
Methods: Immature myeloid cells (HLA-DR-/lowCD33+CD16-) were tested before and after granulocyte colony-stimulating factor (G-CSF) administration in healthy donor and isolated for suppression assays and co-culture with T cells in vitro. Isolated cells were infused in humanized mice for a xenogeneic model of acute GVHD. One hundred allo-HSCT recipients were enrolled prospectively to assess the role of HLA-DR-/lowCD33+CD16- cells in grafts on the occurrence of acute GVHD.
Results: In the present study, G-CSF mobilized HLA-DR-/lowCD33+CD16- cells with immunosuppressive properties in donor peripheral blood. These cells contained more interleukin-10+ and transforming growth factor-beta (TGF-β)+ cells after G-CSF administration and inhibited the proliferation of autologous donor T cells in a TGF-β-dependent manner. Meanwhile, these immature myeloid cells promoted regulatory T cell expansion and induced Th2 differentiation. Importantly, these cells prevented acute GVHD in a humanized mouse model. Moreover, clinical cohort results showed that the number of HLA-DR-/lowCD33+CD16- cells in the donor graft was the only independent risk factor inversely correlated with the incidence of grade II-IV acute GVHD in the recipients (HR 0.388, 95% CI 0.158-0.954, p = 0.039).
Conclusion: HLA-DR-/lowCD33+CD16- cells represent functional MDSCs that may control acute GVHD in allo-HSCT.
Keywords: Acute graft-versus-host disease; Allogeneic hematopoietic stem cell transplantation; Granulocyte colony-stimulating factor; Humanized mouse; Myeloid-derived suppressor cells.