供者CD4^+CD25^+CD127^-调节性T细胞与儿童异基因造血干细胞移植后急性移植物抗宿主病相关研究

Study on relationship between donor CD4^+CD25^+CD127^-regulatory T cells and acute graft versus host disease after allogeneic hematopoietic stem cell transplantation in children

目的:探讨供体移植物CD4+CD25+CD127-调节性T细胞(Treg细胞)表达水平对儿童异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(aGVHD)的影响。方法:采用流式细胞术检测供体淋巴细胞中CD4+CD25+CD127-Treg细胞比例,回顾性分析83例allo-HSCT患儿移植物Treg细胞与移植后aGVHD,其中50例恶性疾病,33例良性疾病。结果 :83例患儿allo-HSCT均获造血重建,其中51例发生0~Ⅰ度aGVHD,32例发生Ⅱ~Ⅳ度aGVHD。发生0~Ⅰ度aGVHD与Ⅱ~Ⅳ度aGVHD患儿移植物Treg细胞比例有统计学差异(3.0%±0.8%比2.5%±1.0%,P=0.030)。中位随访时间286(69~496)d,50例恶性疾病患儿中8例复发,复发与非复发患儿移植物Treg细胞无显著差异(3.2%±0.8%比2.8%±0.8%,P=0.549)。结论:高水平供体移植物Treg细胞有助于降低儿童allo-HSCT后aGVHD发生率,且未增加移植后复发风险;移植物Treg细胞表达量对预测aGVHD有一定意义。

Objective To study the influence of donor CD4＋CD25＋CD127- regulatory T cells （Treg cells） level on acute graft versus host disease （aGVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT） in children. Methods The percentage of CD4＋CD25＋CD127- Treg cells in graft was measured by flow cytometry and the relation between aGVHD and percentage of CD4＋CD25＋CD127- Treg cells in graft were retrospectively analyzed in 83 children with allo-HSCT, including 50 children with malignant disease and 33 with non-malignant disease. Results Engraftment was achieved in all of the 83 children received allo-HSCT. Of them 51 children developed grade 0- [ aGVHD and 32 children developed grade Ⅱ -Ⅳ aGVHD. The percentage of CD4＋CD25＋CD127- Treg cells in graft was significantly higher in patients with grade 0- Ⅰ aGVHD than in patients with grade Ⅱ -Ⅳ aGVHD （3.0%±0.8% vs 2.5%±1.0%, P= 0.030）. After a median follow-up of 286 （69-496） d, 8/50 children with malignant disease relapsed. There was no significant difference in percentage of CD4＋CD25＋CD127- Treg cells in graft between relapsed and non-relapsed cases （3.2%＋_0.8% vs 2.8%＋_0.8%, P=0.549）. Conclusions High level CD4＋CD25＋CD127 Treg cells in graft can reduce the incidence of aGVHD after allo-HSCT without increase in risk of relapse. Percentage of CD4＋CD25＋CD127- Treg cells in graft is a valuable marker for predicting aGVHD after allo-HSCT.