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抑制或删除自身免疫性T细胞对胰岛素生成细胞——β细胞的破坏可以有效预防1型糖尿病的发生.研究表明cTLA4-FasL双功能免疫抑制分子可以抑制T细胞活化及促进T细胞的凋亡.在多次小剂量(40 mg/kg)腹腔注射链脲佐菌素诱导的小鼠自身免疫性糖尿病模型中,初次给予链脲佐菌素的同时,经尾静脉输注(2-5)×108pfu/mL CTLA4-FasL腺病毒进行基因治疗后,糖尿病的发病率显著降低(13％,n=15),血糖和胰岛素水平维持正常;且显著诱导胰腺淋巴细胞凋亡及胰腺淋巴细胞IFN-γ与Vβ8.2TCR的mRNA表达明显下降.表明腺病毒介导CTLA4-FasL基因治疗,有效诱导自身反应性T细胞凋亡,提示其在预防自身免疫性糖尿病的潜在价值.
Inhibition or deletion of autoimmune T cells on insulin-producing cells - β cell damage can effectively prevent the type 1 diabetes mellitus. Studies have shown that cTLA4-FasL bifunctional immunosuppressive molecules can inhibit T cell activation and promote T cell apoptosis. In multiple low-dose (40 mg / kg) intraperitoneal injection of streptozotocin-induced mouse autoimmune diabetes model, the first administration of streptozotocin at the same time, the tail vein infusion (2-5) × The gene therapy of 108pfu / mL CTLA4-FasL adenovirus significantly reduced the incidence of diabetes (13%, n = 15), maintained normal blood glucose and insulin levels, and significantly induced pancreatic lymphocyte apoptosis and pancreatic lymphocyte IFN-γ And Vβ8.2TCR mRNA expression was significantly decreased, suggesting that adenovirus mediated CTLA4-FasL gene therapy, effectively induce autoreactive T cell apoptosis, suggesting its potential value in the prevention of autoimmune diabetes.