allo—HSCT后外周血TH17细胞／Treg细胞的平衡与aGVHD的相关性  

Relationship between helper T cell 17/regulatory T cells balance and acute graft versus host disease after allogeneic hematopoieticstem cell transplantation

作　　者：余碧珍 杜庆华[1] 李庆山[1] 胡婧[1] 王阿慧[2] 邓家德[2] 江雪杰[3] 

机构地区：[1]广州医科大学附属广州市第一人民医院血液科,510180 [2]广州医科大学附属广州市第一人民医院检验科,510180 [3]南方医科大学附属南方医院血液科

出　　处：《中华器官移植杂志》2015年第3期171-175,共5页Chinese Journal of Organ Transplantation

基　　金：广东省自然科学基金（S2013010016726）

摘　　要：目的探讨异基因造血干细胞移植（allo—HSCT）后受者外周血Tnl7细胞／辅助性T淋巴细胞（Treg细胞）平衡与急性移植物抗宿主病（aGVHD）的相关性，以及抗胸腺细胞免疫球蛋白（ATG）对外周血Treg细胞的影响。方法78例接受含或不含ATG预处理的allo-HSCT受者，10例健康志愿者作为对照组。应用流式细胞术检测外周血rrHl7细胞百分比、Treg细胞百分比及T淋巴细胞亚群绝对值，并采用酶联免疫吸附法检测血清THl7细胞相关细胞因子白细胞介素（IL）-17、IL-21、IL-22、IL-23、7干扰素（IFN-7）及转化生长因子81（TGF-β）的水平。结果无aGVHD组和对照组间Treg细胞百分比、THl7细胞百分比及TH17细胞／Treg细胞比值的差异均无统计学意义（P〉0．05）。与对照组和无aGVHD组相比，1～2度aGVHD受者的Treg细胞百分比显著下降，THl7细胞百分比显著增高，THl7细胞／Treg细胞比值显著上升，差异均有统计学意义（P〈0．叭）；随着aGVHD加重，3～4度aGVHD受者的上述差异更为显著（P〈0．01）。aGVHD组IL-17、IL-23、IL-21、IFN-y浓度均高于对照组（P〈0．01）和无aGVHD组（P〈0．05）。aGVHD组较对照组和无aGVHD组血清TGF-~I水平明显下降（P〈0．01）；而aGVHD组与对照组和无aGVHD组间IL-22浓度的差异均无统计学意义（尸〉0．05）。使用ATG者外周血淋巴细胞总数显著低于对照组（P〈0．01）。使用ATG者THl细胞、THl7细胞、CD3’CD4’细胞和非THl／17细胞绝对值显著低于未使用ATG者（P=0．0000），而二者间淋巴细胞总数、CD3’CD4-细胞、TH1／17细胞绝对值的差异无统计学意义（P〉0．05）。结论allo-HSCT后TH17细胞／Treg细胞平衡及相关细胞因子与aGVHD的发生密切相关，ATG影响早期Tnl7细胞和Tnl细胞的重建。Objective To investigate the relationship between the helper T cell 17 （TH 17）/ Regulatory T cells （Treg cells） balance in peripheral blood with acute graft-versus-host reaction （aGVHD） after allogeneic hematopoietic stem cell transplantation （allo-HSCT）, as well as the impact of anti-thymocyte immunoglobulin （ATG） on helper T cells in peripheral blood. Method Seventy- eight hematologic patients underwent allo-HSCT, conditioning with or without ATG. Ten healthy volunteers severed as a control group. The helper T and regulatory T cells in peripheral blood were detected by flow cytometry. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum concentrations of interleukin（IL）-17, IL-21, IL22, IL23, 7 interferon （IFN-~＇）, and transforming growth factor ~1 （TGF-t31）. Result The percentage of Treg cells, TH 17 cells and ratio of TH 17/Treg cells in patients without aGVHD showed no significant difference from the healthy controls （P 0. 05）. As compared with control group and non-aGVHD group, the ratio of Treg cells was increased, the percentage of TH 17 cells, and TH17/Treg cells were significantly increased in 1-2-degree aGVHD group （P〈0. 01）. With increased degree of aGVHD, the difference as above was more significant in 3-4-degree aGVHD recipients （P〈0. 01）. In aGVHD group, the IL-17, IL-23, IL-21 and IFN-γ concentrations were higher than the healthy group （P〈0. 01 ） and non-aGVHD group （P〈 0. 05）. Serum TGF-β1 level in aGVHD group was significantly decreased as compared with healthy group and non-GVHD group （P〈0.05）, while IL-22 concentrations showed no statistically significant difference among three groups （P〉0. 05）. In anti-thymocyte immunoglobulin （ATG） pretreatment group, the absolute count of peripheral blood lymphocytes was less than in healthy control group （P〈0. 01）. In ATG group, the absolute counts of TH l cells, TH 17 cells, CD3＋ CD4＋ cells and non- Tu 1/17 cells were less than in non-ATG group （P

关 键 词：造血干细胞移植 rrHl7细胞 调节性T淋巴细胞 移植物抗宿主病 抗胸腺细胞免疫 球蛋白 

分 类 号：R733.7[医药卫生—肿瘤]