骨髓或外周血中CD4^＋CD25^＋Foxp3^＋调节性T淋巴细胞与aGVHD的关系  

Expression and significance of CD4^＋ CD25^＋ Foxp3 ^＋ T cells in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

作　　者：王晓娟[1] 车传珍 周昱男[1] 刘仲萍[1] 黄士昂[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院干细胞中心,武汉430022 [2]宜昌市五峰土家族自治县人民医院内科

出　　处：《中华器官移植杂志》2009年第8期495-498,共4页Chinese Journal of Organ Transplantation

摘　　要：目的研究患者异基因造血干细胞移植（allo-HSCT）前后骨髓或外周血单个核细胞中CD4^＋CD25^＋Foxp3^＋调节性T淋巴细胞（以下简称CD4^＋CD25^＋Foxp3^＋T细胞）的比率、Foxp3mRNA和Foxp3蛋白的表达与急性移植物抗宿主病（aGVHD）的关系。方法选择37例行HLA相合异基因造血干细胞移植（allo-HSCT））的患者作为研究对象。采用流式细胞术检测患者allo-HSCT前7天（-7d）、移植当天（0d）、移植后30天（＋30d）、＋60d和＋90d时骨髓或外周血单个核细胞中CD4^＋CD25^＋Foxp3^＋T细胞所占的比率：定量聚合酶链反应（PCR）检测Foxp3mRNA相对表达量；蛋白印迹（Western blot）法检测Foxp3的蛋白表达水平。结果37例患者在移植后100d内发生aGVHD13例（aGVHD组），未发生aGVHD24例（无aGVHD组）。CD4^＋CD25^＋Foxp3^＋T细胞的比率在0d时最低，与-7、＋30、＋60、＋90d时比较，差异均有统计学意义（P〈0．01）：与aGVHD组比较，无aGVHD组患者的CD4^＋CD25^＋Foxp3^＋T细胞的比率明显升高，差异有统计学意义（P〈0．01）。aGVHD组患者移植后Foxp3的表达水平逐渐升高，但明显低于无aGVHD组，尤其在＋60和＋90d时的差异有统计学意义（P〈0．01）。Western blot法检测结果表明，aGVHD组受者的Foxp3蛋白表达也明显低于无aGVHD组。结论CD4^＋CD25^＋Foxp3^＋T细胞对防止发生aGVHD具有重要作用，监测患者骨髓或外周血中CD4^＋CD25^＋Foxp3^＋T细胞的比率可以预测aGVHD的发生。Objective To investigate the expression and significance of CD4^＋ CD25^＋ Foxp3^＋ T Cells, Foxp3 mRNA and Foxp3 protein in the acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation （allo-HSCT）. Methods Thirty seven donor grafts and their respective clinical characteristics were evaluated. Flow cytometric analysis was performed to assess the percentage of CD4 ^＋ CD25 ^＋ Foxp3 ^＋ T cells in the recipients before, and 0,30,61）. and 90 days after alloHSCT. The relative expression of Foxp3 mRNA was detected hy real time reverse transcriptionpolymerase chain reaction with aGVHI） as the internal control gene, and the relative expression of Foxp3 protein by Western blot with α- tubulin as the internal control protein. Results aGVHD occurred in 13 out of 37 patients （aGVHD group） ,and the remaining 24 had no aGVHD （no aGVHD group） within 100 days after transplantation. The percentage of CD4^＋ CD25^＋ Foxp3^＋ T cells was the lowest at 0 day of transplantalion with the difference being statistically significant difference in comparison to that at other lime points （ - 7, ＋ 30, ＋ 60,and ＋ 90 days） （P〈0. 01 ）. The percentage of CD4^ ＋CD25 ^＋ Foxp3 ^＋ T cells in no aGVHD group was significantly higher than in aGVHD group （P 〈0. 01）. The expression level of Foxp3 mRNA in aGVHD group was gradually increased after transplantation,but obviously lower than in no aGVHD group, especially at the post transplantation day 61）,and 90,there was significant difference between two group （P〈0. 01 ）. Western blot revealed that the expression of Foxp3 protein in aGVHD group was significantly lower than in no aGVHD group. Conclusion CD4^＋ CD25^＋ Foxp3^＋ T cells may be of importance in preventing the development of aGVHD. Monitoring of the percentage of CD4 ^＋ CD25 ^＋ Foxp3^ ＋ T cells in hone marrow or peripheral blood can predict the occurrence of aGVHD after transplantation.

关 键 词：T淋巴细胞 调节性 基因表达调控 移植物抗宿主病 

分 类 号：R686[医药卫生—骨科学]