胰岛素治疗挽救不了1型糖尿病不断丧失的胰岛数量并避免脆性糖尿病的出现，近年针对1型糖尿病发病机制的免疫治疗研究成为热点，目前报道的1型糖尿病免疫治疗方案可一定程度延缓胰岛功能衰竭速度，但尚不能完全终止免疫损伤进程，其原因主要是阻断的特异性不够和针对的胰岛自身抗原较为单一。为此本研究小组在1型糖尿病临床免疫治疗和致病性T细胞表位前期研究基础上，拟应用IGRP、ZnT8、GAD、INS和IA-2等HLA-2.1限制性胰岛自身抗原表位多肽库扩增1型糖尿病病人外周血中致病性CD8+ T细胞，与人胰岛联合移植至HLA-2.1转基因鼠肾包膜下，建立致病性T细胞致人胰岛免疫损伤的体内评估模型；再以表位多肽库诱导免疫耐受后的转基因鼠淋巴细胞为特异性细胞免疫干预手段，摸索不同表位多肽库对相应抗原特异性致病性T细胞致人胰岛免疫损伤的阻效作用，探讨特异性多靶点细胞免疫治疗方案，为1型糖尿病临床免疫治疗探索新路。

Insulin treatment for type 1 diabetics can not delay progressive loss of islet mass and avoid the occurrence of fragile diabetes during the course of the disease. The research on the immunotherapy based on the immunology mechanism of type 1 diabetes become the hot spot recently years. Current reported protocols of clinical immunotherapy for autoimmune diabetes can delay or decrease the progress of the loss of islet mass, but autoimmunity injury to pancreatic islets can not be stopped completely due to non-antigen speicificity and single autoantigen targeted in the reported studies. Therefore, based on our previous research on clinical immunotherapy with anti-CD20 agent for type 1 diabetes and mapping epitopes of islet antigen specific CD8+ T cell, we design to expand islet autoreactive CD8+ T cell from peripheral blood mononuclear cells of type 1 diabetic patients with HLA-2.1 restricted epitopes pool of islet antigen, such as IGRP, ZnT8, GAD, INS and IA-2. Then the islet antigen epitopic specific T cell and human isolated islets were transplanted under renal capsule membrane of HLA-2.1 transgenic mice, as the evaluation model of immunological injury by autoreactive T cell in vivo. The priming spleenocytes of transgenic mice with epitope peptides pool were transfer to human islets plus autoreactive T cell transplated mice, as multiantigen specific cell immunotherpay. The inhibitory effect of immunological injury were evaluated and compared with different epitope peptides pool. The purpose of the study is to explore the protocol of islet multiantigen specific cell immunotherapy for type 1 diabetes.