Effects of granulocyte-colony stimulating factor on regulatory T cells and related cytokines after allogeneic hematopoietic stem cell transplantation / 中国组织工程研究

ABSTRACT

BACKGROUND: Acute graft-versus-host disease (aGVHD) is an inflammatory disease mediated by regulatory T cells. It is of certain significance to prevent and treat aGVHD by improving the levels of CD4+CD5+regulatory T cells (CD4+CD5+Treg)and related inflammatory factors in the body. OBJECTIVE: To investigate the effect of granulocyte colony stimulating factor (G-CSF) on CD4+CD5+regulatory T cells (CD4+CD5+Treg) and cytokines in children with hematological malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Seventy children with hematological malignancies undergoing allo-HSCT were enrolled. G-CSF was mobilized in the 45 cases (G-CSF group) before allo-HSCT transplantation. The other 25 cases were assigned to non-G-CSF group. Peripheral blood samples were collected at 4 weeks after allo-HSCT. Another 60 healthy children were selected as control group. The levels of T cells, serum interleukin-35 (IL-35) and interferon-γ (INF-γ) were measured by flow cytometry and ELISA, respectively. According to whether aGVHD occurred after allo-HSCT, the 70 cases were divided into aGVHD positive group and aGVHD negative group. The relationship between the changes of T cells and cytokines with aGVHD was analyzed. RESULTS AND CONCLUSION: (1) The percentage of CD4+CD5+Treg in CD4+T and CD4+FoxP3+T cells as well as serum IL-35 level in children with hematological diseases were lower than those in the control group (P < 0.05), while the levels of INF-γ were significantly higher than that in the control group (P < 0.05). (2) The percentage of CD4+CD5+Treg in CD4+T cells and CD4+FoxP3+T cells as well as serum IL-35 level in the G-CSF group were lower than those in the non-G-CSF group (P < 0.05), while the levels of INF-γ was higher than that in the non-G-CSF group (P < 0.05). (3) There were 7 cases (16%) of aGVHD in the G-CSF group and 10 cases (40%) of aGVHD in the non-G-CSF group at 4 weeks after allo-HSCT, and the incidence of aGVHD was significantly different between the G-CSF and non-G-CSF groups (P=0.022). (4) The percentage of CD4+CD5+Treg in CD4+T and CD4+FoxP3+T cells as well as serum IL-35 level in the aGVHD negative group were higher than those in the aGVHD positive group (P < 0.05), while the levels of INF-γ were significantly lower than that in the aGVHD positive group (P < 0.05). (5) CD4+CD5+Treg and CD4+FoxP3+T cells were positively correlated with the IL-35 level, but negatively correlated with the INF-γ level by Pearson single factor analysis. To conclude, G-CSF mobilization can significantly improve CD4+CD5+Treg cells and its transcription factor Foxp3 after allo-HSCT, which may be useful for improving the therapeutic effect of allo-HSCT and preventing aGVHD in patients with malignant hematological diseases.