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

Autor: Pan Suo, Lan-Ping Xu, Yuan-Yuan Zhang, Yu Wang, Yang Zhou, Xiao-Hui Zhang, Kai-Yan Liu, Xiao-Su Zhao, Shu-Zhen Zhai, Zhi-Dong Wang, Ying-Jun Chang, Xiao-Jun Huang, Yan Hong, Meng Lv, Yu-Qian Sun, Dan Liu, Xiang-Yu Zhao, Ke Wang
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
medicine.medical_specialty
Transplantation Conditioning
Regulatory T cell
medicine.medical_treatment
Graft vs Host Disease
chemical and pharmacologic phenomena
Mice
SCID
Hematopoietic stem cell transplantation
Humanized mouse
CD16
lcsh:RC254-282
Granulocyte colony-stimulating factor
Mice
03 medical and health sciences
0302 clinical medicine
Mice
Inbred NOD
immune system diseases
Internal medicine
medicine
HLA-DR
Animals
Transplantation
Homologous
Molecular Biology
Acute graft-versus-host disease
Hematology
lcsh:RC633-647.5
business.industry
Research
Myeloid-Derived Suppressor Cells
Hematopoietic Stem Cell Transplantation
lcsh:Diseases of the blood and blood-forming organs
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Disease Models
Animal
surgical procedures
operative
030104 developmental biology
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Allogeneic hematopoietic stem cell transplantation
Immunology
Myeloid-derived Suppressor Cell
business
Zdroj: Journal of Hematology & Oncology
Journal of Hematology & Oncology, Vol 12, Iss 1, Pp 1-16 (2019)
ISSN: 1756-8722
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13045-019-0710-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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