CD4^+CD25^+FOXP3^+Treg细胞与急性移植物抗宿主病的关系

Relationship between CD4^+CD25^+FOXP3^+Treg cells and acute graft-versus-host disease

背景:CD4+CD25+FOXP3+Treg细胞具有免疫抑制作用,推测可能减少异基因造血干细胞后急性移植物抗宿主病的发生率。目的:观察粒细胞集落刺激因子动员前后,供者外周血CD4+CD25+FOXP3+Treg细胞比率变化,并探讨CD4+CD25+FOXP3+Treg细胞与异基因造血干细胞移植后发生急性移植物抗宿主病的关系。方法:以异基因造血干细胞移植受者90例及其供者为研究对象,供者皮下注射重组人粒细胞集落刺激因子(5μg/kg),1次/12 h,连续5 d后,采集干细胞;分别于动员前后采集供者外周血,流式细胞仪检测其中CD4+CD25+FOXP3+Treg细胞含量,及受者接受移植物中此类细胞含量;根据接受CD4+CD25+FOXP3+Treg细胞数分为高剂量组(细胞比例≥5%)及低剂量组(细胞比例<5%),比较两组移植后急性移植物抗宿主病的发生率。结果与结论:供者在应用粒系集落刺激因子动员前后CD4+CD25+FOXP3+Treg细胞比例分别为11.3%和1.5%,差异有显著性意义(P<0.05);急性移植物抗宿主病阳性组所接受移植物中该群细胞比例为3.4%,阴性组为15.7%,差异有显著性意义(P<0.05);移植造血重建后高剂量组急性移植物抗宿主病的发生率为18.4%,低剂量组急性移植物抗宿主病的发生率为48.1%,二者差异有显著性意义(P<0.05)。因而,粒系集落刺激因子应用能降低正常人外周血中CD4+CD25+FOXP3+Treg细胞比例;CD4+CD25+FOXP3+Treg细胞增加可以降低急性移植物抗宿主病的发生率。

BACKGROUND：The CD4^＋CD25^＋FOXP3^＋Treg cells have immunosuppression effect, and it is speculated that these cells may restrain the occurrence of acute graft-versus-host disease. OBJECTIVE：To observe the variety of the CD4^＋CD25^＋FOXP3^＋Treg cells in the peripheral blood from donors before and after granulocyte colony stimulating factor mobilization, and study the relationship between CD4^＋CD25^＋FOXP3^＋Treg cells and acute graft-versus-host disease. METHODS：Ninety patients with malignant blood diseases who undertook al ogeneic hematopoietic stem celltransplantation and their donors were observed. Granulocyte colony stimulating factor 5μg/kg was injected subcutaneously into the donor per 12 hours for 5 days, and the stem cells were col ected before and after mobilization. The ratio of CD4^＋CD25^＋FOXP3^＋Treg cells in the peripheral blood was detected before and after mobilization with flow cytometry, and the ratio of these cells in the stem cellsuspension was measured by the same method. The patients were divided into two groups according to the CD4^＋CD25^＋FOXP3^＋Treg cells ratio：high dosage group （≥5%） and low dosage group （〈5%）. The incidence of acute graft-versus-host disease was observed in the two groups after transplantation. RESULTS AND CONCLUSION：The ratio of the CD4^＋CD25^＋FOXP3^＋Treg cells in the donor before and after mobilization were 11.3%and 1.5%,respectively, and there was a significant difference （P〈0.05）. The ratio of the CD4^＋CD25^＋FOXP3^＋Treg cells was 3.4%in the patients with acute graft-versus-host disease, and 15.7%in the patients with no acute graft-versus-host disease, showing a significant difference （P〈0.05）. After hematopoietic reconstitution, the incidence of acute graft-versus-host disease was 18.4%in the high dosage group and 48.1%in the low dosage group, and there was a significant difference between the two groups （P〈0.05）. Therefore, the granulocyte colony stimulating factor can lower the ratio of CD4^＋CD25^＋FOXP3^＋Treg cells in the human peripheral blood. The increase in CD4^＋CD25^＋FOXP3^＋Treg cells can restrain the occurrence of acute graft-versus-host disease.