Early myeloid-derived suppressor cells (HLA-DR-/lowCD33+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
Early myeloid-derived suppressor cells (HLA-DR-/lowCD33+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
复制标题
粒细胞集落刺激因子扩增的早期骨髓源性抑制细胞 (HLA-DR(-)/(low)CD33( )CD16(-)) 可预防人源化小鼠的急性移植物抗宿主病 (GVHD)，并可能有助于
DOI：
10.1186/s13045-019-0710-0
复制
发表时间：
2019-03-18
影响因子：
28.5
通讯作者：
Huang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Wang, Ke;Lv, Meng;Huang, Xiao-Jun
简介：髓源性抑制细胞（MDSC）被提议用于控制异基因造血干细胞移植（allo-HSCT）中的移植物抗宿主病（GVHD）。方法：取健康供者，应用粒细胞集落刺激因子（G-CSF）治疗前后的未成熟髓系细胞（HLA-DR（-/low）CD 33（+）CD 16（-）），分离培养，进行抑制试验，并与T细胞共培养。将分离的细胞输注到人源化小鼠中用于异种急性GVHD模型。结果：G-CSF可动员供者外周血中具有免疫抑制特性的HLA-DR（-/low）CD 33（+）CD 16（-）细胞。G-CSF给药后，这些细胞含有更多的白细胞介素-10（+）和转化生长因子-β（TGF-β）（+）细胞，并以TGF-β依赖性方式抑制自体供体T细胞的增殖。同时，这些未成熟的骨髓细胞促进调节性T细胞扩增并诱导Th 2分化。重要的是，这些细胞在人源化小鼠模型中预防急性GVHD。此外，临床队列结果表明，供体移植物中HLA-DR（-/低）CD 33（+）CD 16（-）细胞数量是与受体II-IV级急性GVHD发生率负相关的唯一独立危险因素结论：HLA-DR（-/low）CD 33（+）CD 16（-）细胞代表功能性MDSC，可控制allo-HSCT中的急性GVHD。
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-beta)(+) cells after G-CSF administration and inhibited the proliferation of autologous donor T cells in a TGF-beta-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.