两种不同免疫抑制方案对肾移植受者免疫状态的影响  

The impact of two different immunosuppressive regimens on immune condition in human renal transplant recipients

作　　者：房爱芳[1] 张淦[1] 李永海[1] 向莹[1] 明长生[1] 张伟杰[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所,教育部/卫生和计划生育委员会器官移植重点实验室,湖北武汉100039

出　　处：《实用器官移植电子杂志》2014年第6期344-349,共6页Practical Journal of Organ Transplantation(Electronic Version)

基　　金：国家高技术研究发展计划(863)项目(2012AA021010)

摘　　要：目的通过比较两种不同免疫抑制方案对肾移植术后受者免疫状态的影响,以寻找有利于移植物长期存活的免疫抑制方案。方法研究纳入亲属活体肾移植受者18例,肾功能稳定。根据应用免疫抑制方案的不同分为两组:西罗莫司(SRL)组8例,方案为SRL+吗替麦考酚酯(MMF)+泼尼松(Pred);他克莫司(TAC)组10例,方案为TAC+MMF+Pred;两组用药时间均超过1年。相应的亲属活体肾移植供者作为空白对照。采用流式细胞技术检测3组外周血调节性T细胞(Treg)(CD4+CD25+Foxp3+)、调节性B细胞(Breg)(CD19+CD5+CD1d+)占外周血淋巴细胞的比例,采用酶联斑点免疫试验(ELISPOT)检测SRL组、TAC组肾移植受者外周血淋巴细胞经其相应供者外周血淋巴细胞特异刺激后,分泌特异性细胞因子γ-干扰素(IFN-γ)、白细胞介素-10(IL-10)的单个细胞频数。结果 SRL组肾移植受者外周血CD4+CD25+Foxp3+Treg占总CD4+T细胞的比例为(6.68±0.42)%,TAC组为(3.59±0.47)%,空白对照组为(6.59±0.36)%,SRL组和空白对照组显著高于TAC组(均P<0.05),SRL组与空白对照组比较差异无统计学意义(P>0.05)。SRL组外周血Breg(CD19+CD5+CD1d+)占CD19+B细胞的比例为(16.43±3.56)%,TAC组为(13.09±1.64)%,空白对照组为(16.58±1.31)%,3组之间两两比较差异均无统计学意义(均P>0.05)。ELISPOT检测SRL组分泌IFN-γ的细胞频数为(117.00±21.54)/500 000,TAC组为(126.00±24.08)/500 000;分泌IL-10的细胞频数SRL组为(347.00±55.29)/500 000,TAC组为(249.00±58.97)/500 000,两组比较差异均无统计学意义(均P>0.05)。结论长期应用以SRL为基础的免疫抑制方案并不影响Treg占外周血淋巴细胞的比例,而应用以TAC为基础的免疫抑制方案会降低外周血Treg的数量;两种方案都不影响Breg占外周血CD19+B细胞的比例,而且也不影响受者对供者的特异性反应性。Objective To assess the impacts of sirolimus(SRL)and tacrolimus(TAC)on immune condition <br> in renal transplant recipients,in order to find the optimal immunosuppressive regimens. Methods According to the different immunosuppressive regimens,18 living donor renal transplant recipients with stable renal function were divided into two groups:SRL group(n=8)on SRL + mycophenolate mofetil(MMF)+ prednisone(Pred) and TAC group(n=10)on TAC+MMF+Pred. All the patients received the immunosuppressive regimens for at least one year. The living donors were chosen as the blank control. All the subjects of the 3 groups were examined for the proportion of Regulatory T(Treg)cells(CD4+CD25+Foxp3+)and Regulatory B(Breg)cells(CD19+CD5+CD1d+) in their peripheral blood mononuclear cells(PBMCs)by flow cytometry. After stimulation by the corresponding donor's PBMCs,the recipient's PBMCs were measured through the production of interferon-γ(IFN-γ)and interleukin-10(IL-10)of the recipient's PBMCs of SRL group and TAC group were measured by enzyme-linked immunospot assay(ELISPOT). Results The proportion of CD4+ CD25+ Foxp3+ Treg in the SRL group,TAC group and blank control group were(6.68±0.42)%,(3.59±0.47)%and(6.59±0.36)%,respectively. The ratio of the SRL group and blank control group were significantly higher than that of the TAC group(both P<0.05), and there was no statistically significant difference between the SRL group and blank control group(P>0.05). The proportion of CD19+CD5+CD1d+B cells in the SRL group,TAC group and blank control group were(16.43±3.56)%, (13.09±1.64)%and(16.58±1.31)%,respectively. There were no statistically significant differences among the three groups(all P>0.05). The frequency of the cellsproducing IFN-γin the SRL group and TAC group detected by ELISPOT were(117.00±21.54)/ 500 000 and(126.00±24.08)/ 500 000, without significant difference (P>0.05). The frequency of the cellsproducing IL-10 in the SRL group and TAC group were(347.00±55.29)/500 000 and(249.00±58.97)/ 500 000,without significant d

关 键 词：西罗莫司 他克莫司 调节性T细胞 调节性B细胞 酶联斑点免疫试验 免疫状态 

分 类 号：R699[医药卫生—泌尿科学]