中文摘要：

旨在以非肥胖糖尿病（Non-obese diabetic,NOD）小鼠为动物模型,研究高剂量昆虫细胞表达的重组热休克蛋白gp96（Recombinant gp96,rgp96）对1型糖尿病（Type 1 diabetes,T1D）的预防作用。以高剂量rgp96免疫NOD小鼠,用血糖仪监测小鼠血糖值,用流式细胞术检测小鼠脾脏CD4~＋CD25~＋Foxp3~＋调节性T细胞（Regulatory T cells,Tregs）亚群频率,然后用一系列体外实验探究高剂量rgp96对Tregs的影响。结果显示高剂量rgp96免疫有效地预防或延缓小鼠T1D发病,免疫诱导Tregs数量明显增加。体外实验发现rgp96蛋白促进Tregs增殖,诱导Foxp3表达上调和IL-10分泌增加。研究结果为开发基于rgp96的新型T1D预防和治疗性疫苗提供了依据。

英文摘要：

Type 1 diabetes（T1D）,the most prevalent human autoimmune disease,occurs in genetically susceptible individuals.Regulatory T cells（Tregs） are defective in T1 D setting.Therefore,efforts to repair or restore Tregs in T1 D may prevent or reverse this autoimmune disease.Here,we studied the potential role of rgp96 in preventing T1 D,using non-obese diabetic（NOD） mice as an animal model.High-dose rgp96 immunization elicited efficient protection of mice against T1 D,as evidenced by stable blood glucose,decreased disease incidence.Significantly increased CD4~＋ CD25~＋ Foxp3~＋ Tregs were observed in immunized mice.In vitro co-culture experiments demonstrated that rgp96 stimulation enhanced Treg proliferation and suppressive function by up-regulation of Foxp3 and IL-10.Our work shows that activation of Tregs by high-dose rgp96 immunization protects against T1 D via inducing regulatory T cells and provides preventive and therapeutic potential for the development of an rgp96-based vaccine against T1 D.