人胰岛移植长期疗效尚不理想,主要原因之一是移植后自身免疫糖尿病复发(T1DR)，而抗免疫排斥药不能阻止自身免疫对胰岛的损伤。锌转运体8抗体(ZnT8A)已用于1型糖尿病（T1D）诊断，ZnT8特异性CD8+T细胞(ZnT8-CD8+T)是T1D胰岛自身免疫损伤的原因之一。最新研究发现ZnT8A可预测T1DR,而ZnT8-CD8+T是否直接参与T1DR发病尚不清楚。故我们拟在前期ZnT8研究基础上，拟通过MHC-I四聚体技术筛选并构建ZnT8-CD8+T,以NOD.β2mnull.HHD转基因鼠为胰岛移植模型,探讨ZnT8-CD8+T在T1DR发病中的作用,寻找T1DR早期免疫诊断标志。而我们前期研究发现调节性T细胞(Treg)可以抑制效应性T细胞导致的胰岛移植急性排斥反应，故拟进一步探讨Treg是否可通过抑制ZnT8-CD8+T的致病性，延长胰岛移植物存活时间，为胰岛移植免疫干预打下基础

Islet allografts are subject both to conventional allograft immunity and to type 1 diabetes recurrence (T1DR). There is no immunosuppression that so far has controlled the progression of islet autoimmunity. ZnT8 is a major autoantigen of type 1 diabetes. MHC-I-restricted CD8 T cells play a central role in type 1 diabetes autoimmune pathogenesis. However, it is unclear how host ZnT8-MHC-I-restricted autoreactive CD8 T cells may also contribute to the recognition of allogeneic islet grafts that express disparate MHC class I molecules. We hypothesized that ZnT8-specific CD8 T cells can target MHC-mismatched islet allografts. To test this hypothesis, we determined whether ZnT8-specific CD8 T cells could damage MHC-mismatched islets independent of conventional allograft immunity and be vulnerable to autoimmune pathogenesis. Regulatory T cells(Tregs) suppress naive T cell responses, prevent autoimmunity, and delay allograft rejection. It is not known, however, whether Tregs suppress autoimmune disease recurrence mediated by ZnT8-specific CD8+ T cells after islet transplantation. Our findings could lead to the development of new therapies to improve islet graft survival and protect beta cells from the immune system in patients with type 1 diabetes.