CD4^＋CD25^High调节性T细胞及负调控因子白细胞介素-10与异基因造血干细胞移植后移植物抗宿主病的关系研究

Association of CD4^＋CD25^High regulatory T cells and the negative control factor IL-10 with the development of acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

目的 研究异基因造血干细胞移植（allo-HSCT）后患者外周血CD4^＋CD25^High调节性T细胞（Treg细胞）及细胞因子白细胞介素-10（IL-10）与急性移植物抗宿主病（aGVHD）的关系.方法 采用流式细胞术检测13例allo-HSCT后患者外周血CD4^＋CD25^HighFoxp3^HghTreg细胞、CD4^＋CD25^HighCD^127LowTreg细胞占CD^4＋T细胞的百分含量,同时用酶联免疫吸附法（ELISA）检测对应时期血清中IL-10的质量浓度.结果 13例患者均获得造血功能重建;aGVHD组CD4^＋CD25^HighCD127^Low/CD4^＋与CD4^＋CD25^HighFoxp3^High/CD4^＋比例均明显低于无GVHD组,差异有统计学意义（P＜0.01）;Ⅲ～Ⅳ度aGVHD亚组CD4^＋CD25^HighCD^127Low/CD4^＋与CD4^＋CD25^HighFoxp^3High/CD4^＋比例低于Ⅰ～Ⅱ度aGVHD亚组,但差异无统计学意义（P＞0.05）;相同组别间CD4^＋CD25^HighCD^127Low/CD4^＋与CD4^＋CD25^HighFoxp^3High/CD4^＋差异无统计学意义.aGVHD组的IL-10质量浓度明显低于无GVHD组,差异有统计学意义（P＜0.01）.Treg细胞与IL-10变化呈相关性（r=0.925,P＜0.05）.结论 Treg细胞的水平与allo-HSCT后aGVHD的发生有密切关系;通过监测Treg细胞水平对临床早期诊断aGVHD及判断aGVHD预后、指导免疫调节剂的应用具有重要意义;CD127^Low可以作为Treg细胞表面的特异标志,推进对Treg细胞的检测及分离纯化;IL-10是一种重要的负调控因子;Treg细胞与IL-10的表达在aGVHD患者存在相关性,可能为Treg细胞的免疫抑制机制提供一定基础.

Objective To investigate the relationship between the CD4^＋CD25^High regulatory T cells and cytokine IL-10 and acute graft-versus-host disease （aGVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods Flow cytometric was used to detect the percentage of CD4^＋CD25^High Foxp^3Hiht Treg cell and CD4^＋CD25^HighCD^127LowTreg cell in CD4^＋ T cells and at the same time ELISA was used to test the serum IL-10 levels in corresponding period. Results 13 patients have received hcmatopoietic function reconstruction, aGVHD group of CD4^＋CD25^HighCD127^Low/CD25^HighFoxp3^High/CD4^＋ ratio were significantly lower than non-aGVHD group, the difference was statistically significant （P 〈0.01）; Ⅲ～Ⅳ degree of aGVHD subgroup was lower than Ⅰ～Ⅱ degree of aGVHD subgroup, but no statistical significance（P 〉0.05）; the same as between-group CD4^＋CD25^HighCD127^Low/CD4^＋ and the CD4^＋CD25^HighFoxp3^High/CD4^＋ has no significant difference; aGVHD group of IL-10 concentration was significantly lower than non-GVHD group, the difference was statistically significant （P 〈0.01）. Treg cell and IL-10 changes in correlation, r = 0.557, P 〈0.05. Conclusion The level of Treg cell was closely related to the occurrence of aGVHD after allo-HSCT. So it is very important to monitor the Treg cell level for clinical carly diagnosis of aCVHD and predict prognosis of aGVHD and guide the application of immunosuppressant. CD127 can serve as a Treg cell surface-specific marker, to promote the detection of Treg cell and purification. IL-10 was an important negative regulator. Treg cell and IL-10 expression in patients with aGVHD was correlation, which may provide some basis for Treg cell immunosuppressive mechanism.