I型糖尿病（T1D）是CD4T细胞依赖的自身免疫疾病，淋巴细胞浸润导致分泌胰岛素的胰岛β细胞损伤，其确切的发病机制尚不明确。T1D中针对自身抗原的CD4T细胞免疫反应持续发生形成记忆性CD4T细胞（Tm），但目前CD4Tm细胞对T1D发病的作用尚无研究报道。.本实验室前期研究首次发现伴随T1D病程，CD4Tm细胞在T1D小鼠外周血中显著增加，且胰腺组织中明显的浸润了一群CD4Tm细胞，而CD8Tm细胞无显著变化；更为重要的是T1D病人外周血中CD4Tm细胞显著增加。本项目拟通过免疫蛋白组学等方法比较研究T1D小鼠及病人中病理性CD4Tm细胞与正常CD4Tm细胞的功能及其表达的分子,找出与T1D发病直接相关的分子，研究结果将揭示CD4Tm细胞诱导T1D及其迁移至胰腺组织的作用机制，为T1D的发病机制提供新的思路，利用中和抗体封闭新发现的分子有可能成为预防和治疗T1D的有效方法。

Type I diabetes (T1D) is an CD4 T cell-dependent autoimmune disease and results from lymphocytes infiltration and destructin of insulin-producing β cells in pancreatic islets. The exact mechanism of T1D is still unclear. T cell immune response react to self antigen sostenuto occur which definitely produce memory T cells. But the research about the effect of CD4Tm cells on T1D is rarely..Our previous results firstly showed following the process of T1D, the percentage of CD4Tm cells in blood of T1D mouse increased and there is a CD4Tm cell population clearly infiltrated into pancreas. However, there is no differences among CD8Tm cells. In this project, the comparison of function and differential molecules expression of the pathological CD4Tm cells in T1D with those from normal CD4Tm cells will be performed by immunoproteomics. We aimed to find new molecules directly related to T1D. The results will reveal the mechanism of T1D induction by CD4Tm cells and CD4Tm cells migration into pancreases, which will provide new sights for the mechanism of T1D pathogenesis. The neutralizing antibodies blocking the new molecules will be potential effective methods for T1D prevention and therapy.