Yoon J W
Laboratory of Viral and Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Alberta, Canada.
Diabete Metab. 1992 Sep-Oct;18(5):378-86.
Genetic factors and environmental factors are thought to be involved in the pathogenesis of insulin-dependent diabetes mellitus Type 1. Viruses, as one environmental factor, may act as primary injurious agents to beta cells or as triggering agents for autoimmunity. Some viruses such as EMC-D and Coxsackie B4 can induce Type 1 diabetes by infecting and destroying beta cells in genetically susceptible mice. In addition, certain species of monkey, such as Patas, show elevated blood glucose levels and depressed insulin secretion after infection with Coxsackie B4 virus. An occasional case of Type 1 diabetes mellitus appears to be associated with the infection of beta cells with Coxsackie B viruses. In addition, Coxsackie B4 virus may also generate viral antigen-specific cytotoxic T cells which may cross-react with a beta cell-specific autoantigen leading to autoimmune Type 1 diabetes. In the case of viral triggering of autoimmune Type 1 diabetes, certain viruses (eg, retrovirus in NOD mice and rubella virus in hamsters and humans) may alter a normally existing beta cell antigen into an immunogenic form or might induce a new antigen, leading to beta cell-specific autoimmune insulin dependent diabetes mellitus. In addition, other viruses (eg, Kilham's rat virus in DR-BB rats) could generate antigen-specific T effector cells which may cross-react with a beta cell-specific autoantigen. In contrast to the induction of diabetes, viruses can prevent the development of diabetes. Inoculation of DP-BB or NOD mice with lymphocytic choriomeningitis virus reduced the incidence of diabetes or prevented the disease by disordering particular lymphocyte subsets.(ABSTRACT TRUNCATED AT 250 WORDS)
遗传因素和环境因素被认为与1型胰岛素依赖型糖尿病的发病机制有关。病毒作为一种环境因素,可能是β细胞的主要损伤因子,也可能是自身免疫的触发因子。一些病毒,如脑心肌炎病毒(EMC-D)和柯萨奇B4病毒,可通过感染和破坏基因易感小鼠的β细胞来诱发1型糖尿病。此外,某些种类的猴子,如赤猴,感染柯萨奇B4病毒后会出现血糖水平升高和胰岛素分泌减少的情况。偶尔有1型糖尿病病例似乎与柯萨奇B病毒感染β细胞有关。此外,柯萨奇B4病毒还可能产生病毒抗原特异性细胞毒性T细胞,这些细胞可能与β细胞特异性自身抗原发生交叉反应,导致自身免疫性1型糖尿病。在病毒触发自身免疫性1型糖尿病的情况下,某些病毒(如非肥胖糖尿病(NOD)小鼠中的逆转录病毒以及仓鼠和人类中的风疹病毒)可能会将正常存在的β细胞抗原转变为免疫原性形式,或者可能诱导产生新的抗原,从而导致β细胞特异性自身免疫性胰岛素依赖型糖尿病。此外,其他病毒(如糖尿病抗性(DR)-BB大鼠中的基尔汉姆大鼠病毒)可产生抗原特异性T效应细胞,这些细胞可能与β细胞特异性自身抗原发生交叉反应。与诱发糖尿病相反,病毒可以预防糖尿病的发生。用淋巴细胞性脉络丛脑膜炎病毒接种DP-BB或NOD小鼠可降低糖尿病的发病率,或通过扰乱特定淋巴细胞亚群来预防疾病。(摘要截选至250字)