STUDIES OF COXSACKIEVIRUS-INDUCED MYOCARDITIS

小鼠接种柯萨奇病毒B3(CVB3)导致心肌炎， 局灶性单个核细胞对病毒感染细胞的炎症反应 心脏组织。涉及细胞毒性T细胞的迟发型超敏反应 淋巴细胞对病毒诱导的表面抗原(新抗原)的反应(S) 都与这一人类疾病的极佳模型有关。我们建议 用特异性免疫荧光法鉴定心脏细胞 感染并携带新抗原的组织(S)和单核细胞 心肌炎形成过程中对新抗原反应的细胞类型(S) 损伤。CVB3病毒感染的小鼠新生皮肤成纤维细胞(MNSF) 作为CVB3接种的心肌炎小鼠CTL的靶点，表明 新抗原的存在(S)。我们将使用MNSF作为组织培养源 新抗原(S)的分离、鉴定和鉴定。 各种生化和免疫学技术。单克隆抗体 将针对MNSF新抗原(S)开发用于颞叶肿瘤研究 巨噬细胞集落刺激因子表面与病毒相关的新抗原S的出现 复制，遗传来源，表达心脏细胞的类型 新抗原(S)和新抗原(S)在疾病过程中的作用。我们会 鉴定和确定血清中一种因子(S)的作用机制 对CVB3诱导的心肌炎具有抵抗力的小鼠，在转移到 正常小鼠，给予保护。我们将调查其中的机制 预防性抗CVB3抗体的抗独特型抗血清 改善CVB3诱导的心肌炎。An的作用机制 将对抗心肌碱类似物进行评估。可能起到的作用 在预防心肌炎中的抑制细胞将使用 X-射线照射的小鼠供体或受体和几种类型的淋巴细胞 对CVB3诱导的心肌炎耐药的小鼠。在上述所有内容中 研究，一个独特的等基因心肌炎或心肌炎集合 CVB3的变种将被用来提供关于 新抗原(S)、抑制细胞的可能作用和新抗原的类型 单个核细胞参与心肌炎。我们将使用生化技术 方法确定心肌炎患者之间的毒力差异 而CVB3的心肌病变种可以归因于 衣壳多肽(S)。

Inoculation of mice with coxsackievirus B3 (CVB3) results in myocarditis, a focal mononuclear cell inflammatory response to virus-infected cells in heart tissue. Delayed hypersensitivity responses involving cytotoxic T lymphocyte (CTL) reactions to viral-induced surface antigens (neoantigen(s) are implicated in this excellent model for the human disease. We propose to use specific immunofluorescence assays to identify the cells in heart tissue that become infected and bear the neoantigen(s) and the mononuclear cell types that respond to neoantigen(s) during formation of myocarditic lesions. Murine neonatal skin fibroblasts (MNSF) infected with CVB3 serve as targets for CTL from CVB3-inoculated myocarditic mice, indicating the presence of neoantigen(s). We will use MNSF as a tissue culture source for neoantigen(s) and identify, isolate and characterize the neoantigen(s) by a variety of biochemical and immunological techniques. Monoclonal antibodies will be developed against MNSF neoantigen(s) for use in studies on temporal appearance of neoantigen(s) on the surface of MNSF relative to virus replication, genetic origin, type of heart cell expressing the neoantigen(s) and role of neoantigen(s) in the disease process. We will identify and determine the mechanism of action of a factor(s) in sera from mice resistant to CVB3-induced myocarditis which can, upon transfer to normal mice, confer protection. We will investigate the mechanism by which anti-idiotypic antiserum against anti-CVB3 antibody prophylactically ameliorates CVB3-induced myocarditis. The mechanism of action of an antimyocarditic base analogue will be assessed. The possible role of suppressor cells in preventing myocarditis will be examined using x-irradiated murine donors or recipients and lymphocytes from several types of mice resistant to CVB3-induction of myocarditis. In all of the above studies, a unique collection of isogenic amyocarditic or myocarditic variants of CVB3 will be used to provide information on the nature of the neoantigen(s), the possible role of suppressor cells and the types of mononuclear cells participating in myocarditis. We will use biochemical methods to determine whether differences in virulence between amyocarditic and myocarditic variants of CVB3 can be attributed to differences in a capsid polypeptide(s).