本研究拟关注不同免疫抑制剂对肾移植受者CD4+T细胞GAL-9/CEACAM1/TIM-3/BAT3信号通路对Th1/Th2、Th17/Treg细胞活化和耐受的调节作用。基于免疫抑制剂对移植患者T细胞亚群平衡偏移及负性分子调控作用的前期研究及预实验结果，推测使用他克莫司的肾移植受者高表达的BAT3分子抑制了负性分子GAL-9/CEACAM1/TIM-3通路活性，致Th1/Th2，Th17/Treg平衡偏移，Th1及Th17活跃，Treg受抑，受者处于慢性炎症状态，是导致慢性移植物失功的重要因素；雷帕霉素可调节负性分子GAL-9/CEACAM1/TIM-3通路高表达，使BAT3分子解离，Th1及Th17功能受抑，Treg功能活跃，可有效逆转慢性移植物失功受者CD4+T细胞亚群平衡偏移，拟证实药物调控GAL-9/CEACAM1/TIM-3/BAT3信号通路是治疗肾移植慢性移植物失功的重要靶点。

This study focuses on the regulatory effect of different immunosuppressants on Th1/Th2, Th17/Treg cell activation and tolerance via GAL-9/CEACAM1/TIM-3/BAT3 signaling pathway of CD4+T cell. Based on the results of our previous studies on regulatory effect of immunosuppressants on T cell subsets imbalance and negative molecules in transplant recipients as well as our pilot study, we speculate that the increased expression of BAT3 in renal transplant recipients with tacrolimus would inhibit the activity of negative molecules GAL-9/CEACAM1/TIM-3 pathway and induce the imbalance of Th1/Th2，Th17/Treg, including increased activity of Th1 and Th17 as well as inhibition of Treg, which would result in the chronic inflammation status of the recipients and contribute to chronic allograft dysfunction; Meanwhile, sirolimus could increase the expression of negative molecules GAL-9/CEACAM1/TIM-3 pathway and induce the detachment of BAT3, which would cause the inhibition of Th1, Th17 and stimulation of Treg so that the imbalance of CD4+T cell subsets of recipients with chronic allograft dysfunction could be reversed effectively. By figuring out such regulatory mechanism, we hope to prove that regulating GAL-9/CEACAM1/TIM-3/BAT3 signaling pathway by immunosuppressants is an important therapeutic target of renal transplant recipients with chronic allograft dysfunction.