移植排斥是同种胰岛移植的主要障碍，靶向干预效应细胞是阻止/减轻胰岛移植排斥反应的有效措施。前期研究发现，基因敲除和免疫毒素（M290-SAP）清除CD103表达细胞能促进同种胰岛移植物的存活，证明CD103表达细胞在排斥反应中发挥重要作用。然而，上述方法存在应用缺陷，因此需探寻新的有效手段。目前，我们已成功制备了抗体药物偶联物（Antibody-drug conjugate, ADC）M290-MC-MMAF，它能高效低毒地靶向清除CD103表达细胞，并能显著延长同种胰岛移植物的存活时间。在此工作基础上，本项目应用同种胰岛移植模型，用免疫分子生物学技术，从CD103/E-cadherin信号途径及CD4（Th1/Th2/Th17/Treg）和CD8 T细胞免疫系统再平衡入手，研究CD103表达细胞清除对胰岛移植的影响，阐明其作用机制，为同种胰岛移植抗排斥反应治疗提供新的理论依据和干预手段。

Transplant rejection is a major obstacle to the allogeneic islet transplantation. Targeted intervention of effector cells is an effective measure to prevent / reduce islet allograft rejection. Previous studies found that knockout and immunotoxins (M290-SAP) could promote the survival of pancreatic islet allografts by removal of CD103-expressing cells, which demonstrated that CD103-expressing cells play an important role in the rejection. However, the methods described above have defects in the application; it is necessary to find new effective means to overcome these drawbacks. Currently, we have successfully prepared antibody-drug conjugate (ADC) M290-MC-MMAF. It eliminates CD103 -expressing cells with high efficiency and low toxicity, and can significantly prolong the survival time of pancreatic islet allografts. In the present study, we will utilize the ADC into islet transplantation models to observe its influence on rejection and elucidate the underlying mechanisms focused on CD103 / E-cadherin signaling and rebalancing of the immune system of CD4 (Th1/Th2 /Th17/Treg) and CD8 T cells. In general, this project will provide new theoretical basis and viable strategy for therapeutic intervention in islet allograft rejection.