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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2019

Open Access 01-12-2019 | Filgrastim | Research

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

Authors: Ke Wang, Meng Lv, Ying-Jun Chang, Xiang-Yu Zhao, Xiao-Su Zhao, Yuan-Yuan Zhang, Yu-Qian Sun, Zhi-Dong Wang, Pan Suo, Yang Zhou, Dan Liu, Shu-Zhen Zhai, Yan Hong, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang

Published in: Journal of Hematology & Oncology | Issue 1/2019

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Abstract

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.
Appendix
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Metadata
Title
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
Authors
Ke Wang
Meng Lv
Ying-Jun Chang
Xiang-Yu Zhao
Xiao-Su Zhao
Yuan-Yuan Zhang
Yu-Qian Sun
Zhi-Dong Wang
Pan Suo
Yang Zhou
Dan Liu
Shu-Zhen Zhai
Yan Hong
Yu Wang
Xiao-Hui Zhang
Lan-Ping Xu
Kai-Yan Liu
Xiao-Jun Huang
Publication date
01-12-2019

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