他克莫司与环孢菌素A对肝移植受者CD4/CD8 T淋巴细胞亚群及共刺激分子的调节作用

Regulatory function of tacrolimus and CsA on CD4/CD8 T lymphocyte subgroups and costimulators on them in allo-liver recipients

目的:探讨他克莫司(Tacrolimus,FK506)与环孢菌素A(CsA)对肝移植受者T淋巴细胞亚群共刺激分子的调节作用。方法:采用荧光标记单克隆抗体(mAb)结合流式细胞技术,测定移植术后使用FK506或CsA治疗2月末的肝移植受者外周血T细胞亚群及其表面共刺激分子CD28、CD152和ICOS的表达情况。以健康志愿者(健康对照组)和患终末期肝脏疾病拟进行肝移植者(疾病对照组)为对照。结果:疾病对照组T细胞亚群平衡紊乱、共刺激分子表达异常(P<0.05)。治疗组肝移植受者T淋巴细胞亚群表达恢复至健康对照水平,T细胞表面CD28和ICOS分子表达显著降低(P<0.05)而CD152分子表达明显升高(P<0.05)。比较不同药物治疗组:CsA治疗组CD4+T细胞表达和CD8+T细胞表面CD28、CD152分子表达均明显高于FK506治疗组(P<0.05);其他指标无统计学意义(P>0.05)。结论:在常规血药浓度条件下FK506和CsA的对CD4/CD8T细胞亚群及共刺激分子的免疫调节作用存在差异。FK506对T细胞亚群的调节作用强于CsA。FK506可同时抑制正性共刺激分子CD28和ICOS表达并促进负性共刺激分子CD152表达,而CsA对T细胞免疫抑制作用主要是通过促进CD152分子的高表达介导。

AIM：To explore the regulatory function of FK506 and CsA on CD4/CD8 T lymphocyte subgroups and co-stimulators on them.METHODS：The fluorescein-labelled monoclonal antibodies and flowcytometer were used to determine the T-lymphocyte subgroups and the expression of CD28,CD152 and ICOS on them in allo-liver recipients treated with FK506 or CsA at the end of 2 months after transplantation and treatment.Healthy volunteers and the patients who suffered from severe hepatic diseases and would receive liver transplantation were used as controls.RESULTS：In disease-control group,the balance of T cell subgroups was disturbed and the expression of co-stimulators was abnormal.In liver recipients receiving immunosuppressive therapy,the expression of T-cell subgroups returned to the normal level,the expressions of CD28 and ICOS on T cells decreased significantly（P〈0.05）,while the expression of CD152 on T cells increased significantly（P〈0.05）.Between two treatment group,the expression of CD4＋T cells and the expression of CD28 and ICOS on CD8＋T cells in CsA-treated group were much higher than those in FK506-treated group（P〈0.05）,and there was no significant difference between two treatment groups in other indexes.CONCLUSION：At routine blood concentration,there is some difference in the regulatory effect of FK506 and CsA on T-cell subgroups and the expression of co-stimulators on T cells.The regulatory effect of FK506 on T-cell subgroups is stronger than that of CsA.FK506 can not only inhibit the expression of positive co-stimulatory molecules CD28 and ICOS but also promote the expression of negative co-stimulatory molecule CD152,while CsA can exert its immunosuppressive effect mainly through promoting the expression of CD152.