诱导长期T细胞免疫耐受是1型糖尿病(T1D)免疫治疗的主要目标。目前大多数的免疫治疗方案因疗效不确定或存在相关的副反应而未能达到预期目标。最近研究表明纳米微粒修饰的表位能够有效的诱导实验性自身免疫脑脊髓膜炎（EAE）小鼠产生长期免疫耐受，预防和治疗EAE的发生和进展。因此申请人在前期1型糖尿病致病性T细胞表位研究的基础上，观察了纳米微粒修饰的ZnT8或IGRP的混合表位在HLA-A2.1转基因鼠体外和体内能否减轻或阻止抗原表位特异性T细胞反应及其可能的机制。同时应用纳米微粒修饰的表位预处理人的ZnT8或IGRP的CD8+T细胞克隆与人胰岛体外共培养，进一步分析处理过后的CD8+T细胞对人胰岛的攻击能力。最后筛选相应表位阳性的T1D患者，进一步证明纳米微粒修饰致病性T细胞表位对T1D患者外周血中致病性T细胞反应的影响。本研究将纳米技术引入免疫耐受的治疗方案，为T1D免疫治疗探索新的思路。

The induction of long-lasting T cell tolerance is a primary goal of therapies for type 1 diabetes (T1D). Many strategies have attempted to achieve this goal. However, they have had limited success and have been associated with adverse effects. Recent study showed that epitope-coupled particles(500nm) can safely induce tolerance in experimental autoimmune encephalomyelitis (EAE) and could have broad utility in a range of immune disorders. Our previous research found three major pathogenic CD8+ T cell epitopes derived from ZnT8. Therefore, based on our study, we will design to observe if nanoparticles bearing ZnT8 or IGRP epitopes could safely induce long-lasting T cell tolerance and attenuate disease in T1D. As evaluation of epitope-coulpled particles involved in induction of T cell tolerance, antigen specific T cell responses will be detected from immunized mice in vitro or from mice with epitope-coupled particles intravenous injection and explore the possible mechanism. Then the antigen-specific CTL will be evaluated by cocultured with T cell clones and human isolated islets after treated with ZnT8 or IGRP epitope-coulpled particles. Furthermore, antigen-specific T cells in T1D patients will be analyze after treated with epitope-coulpled particles in vitro. The purpose of the study is to demonstrate antigen attached to nanoparticles could induce tolerance in T1D. It will explore new ideas of clinical immunotherapy for T1D.