CAR PROTEIN AND AUTOIMMUNITY

汽车蛋白与自身免疫

• 批准号: 6221356
• 负责人: Robert William Finberg
• 金额: $ 15.6万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-05 至 2003-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6221356
• 关键词: Adenoviridae; Coxsackievirus; HeLa cells; antigen antibody reaction; autoimmune disorder; chemokine; confocal scanning microscopy; cytokine receptors; diabetes mellitus; electron microscopy; enzyme linked immunosorbent assay; flow cytometry; genetically modified animals; human tissue; immune response genes; laboratory mouse; myocarditis; pathologic process; polymerase chain reaction; protein structure function; receptor expression; virus infection mechanism; virus protein; virus receptors

Many auto-immune diseases are thought to be triggered by viral infections. In particular auto-immune diabetes and myocarditis are said to follow infections with enteroviruses. Histopathologic studies indicate that mumps and adenoviruses are viruses associated with myocarditis. In addition the Group B Coxsackie viruses have been isolated from patients who subsequently develop diabetes or myocarditis. Studies of humans with acute myocarditis and diabetes indicate the infiltrating T cells have a restricted usage of T-cell receptor genes suggesting that they may be directed at a particular antigen. Animal models indicate that both auto-immune diabetes and myocarditis can be initiated by Coxsackie B viruses. In addition to evidence that T cells can transfer the disease, a role of cytokines has been postulated for auto-immune diabetes and myocarditis. Studies in knock-out mice indicate a role for chemokines in the initiation of the inflammatory process that leads to Coxsackie B virus induced myocarditis. Hypotheses concerning the pathogenesis of auto-immune responses have generally focused on either a viral epitope mimicking a cellular protein (e.g. the GAD protein and a Coxsackie B4 protein), or suggested that the inflammatory response stimulated by the infectious event might damage the cell causing inflammatory changes that subsequently result in the generation of an immune response to host tissues. Whether the inflammation stimulates T cells that recognize host proteins or there is persistence of viral proteins has been hard to define in most model systems. In addition it is unclear how the type of auto- immune response relates to the tropism of the viral agent. We have recently defined a host cell surface protein that serves as the receptor for all group B Coxsackie viruses, the fiber binding protein of most adenoviruses, and a major determinant in mumps infection. The distribution of this protein suggests that its expression correlates with the ability of these viruses to induce auto-immune diseases. We plan to define the role of this protein in the induction of auto-immune disease and use transgenic and knock-out mice to define the mechanisms by which viruses stimulate autoimmune responses.

人们认为许多自身免疫性疾病是由病毒感染引起的。 尤其是自身免疫性糖尿病和心肌炎遵循肠病毒感染。组织病理学研究表明，腮腺炎和腺病毒是与心肌炎相关的病毒。 此外，B组Coxsackie病毒已从随后患糖尿病或心肌炎的患者中分离出来。 对急性心肌炎和糖尿病的人类的研究表明，浸润的T细胞的使用有限使用T细胞受体基因，这表明它们可能针对特定的抗原。 动物模型表明，自身免疫性糖尿病和心肌炎都可以由Coxsackie B病毒引发。 除了证据表明T细胞可以转移疾病外，还假定细胞因子的作用是自身免疫性糖尿病和心肌炎。 在敲除小鼠中的研究表明，趋化因子在炎症过程的启动中的作用，导致Coxsackie B病毒诱导心肌炎。关于自动免疫反应的发病机理的假设通常集中在模仿细胞蛋白（例如GAD蛋白和Coxsackie B4蛋白）的病毒表位上，或表明由感染事件刺激的炎症反应可能会损害炎症会导致炎症导致不受其反应的造成抗反应的炎症，从而损害了一代人的造成造成的反应，从而造成了一代人的造成一代人的造成一代人。 在大多数模型系统中，炎症是刺激识别宿主蛋白的T细胞还是病毒蛋白的持久性。 此外，尚不清楚自动免疫反应的类型与病毒剂的向性关系如何相关。 我们最近定义了一种宿主细胞表面蛋白，该蛋白充当所有B组Coxsackie病毒，大多数腺病毒的纤维结合蛋白以及腮腺炎感染中的主要决定因素。 该蛋白质的分布表明其表达与这些病毒诱导自身免疫性疾病的能力相关。 我们计划定义该蛋白在诱导自动免疫疾病中的作用，并使用转基因和敲除小鼠来定义病毒刺激自身免疫反应的机制。