Early myeloid-derived suppressor cells (HLA-DR(−)/(low)CD33(+)CD16(−)) expanded by granulocyte colony-stimulating factor prevent acute graft-versus-host disease (GVHD) in humanized mouse and might contribute to lower GVHD in patients post allo-HSCT

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(−/low)CD33(+)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(−/low)CD33(+)CD16(−) cells in grafts on the occurrence of acute GVHD. RESULTS: In the present study, G-CSF mobilized HLA-DR(−/low)CD33(+)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(−/low)CD33(+)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(−/low)CD33(+)CD16(−) cells represent functional MDSCs that may control acute GVHD in allo-HSCT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13045-019-0710-0) contains supplementary material, which is available to authorized users.