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.
J Hematol Oncol
; 12(1): 31, 2019 03 18.
Article
em En
| MEDLINE
| ID: mdl-30885244
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-ß)+ cells after G-CSF administration and inhibited the proliferation of autologous donor T cells in a TGF-ß-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante Homólogo
/
Fator Estimulador de Colônias de Granulócitos
/
Transplante de Células-Tronco Hematopoéticas
/
Condicionamento Pré-Transplante
/
Células Supressoras Mieloides
/
Doença Enxerto-Hospedeiro
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
J Hematol Oncol
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China