Analysis of experimental autoimmune myositis and its immunotherapy

为了解人类多发性肌炎的发病机制，用部分纯化的肌球蛋白免疫Lewis大鼠诱导实验性自身免疫性肌炎(EAM)，并用CDR3分型分析EAM诱导的T细胞的T细胞受体(TCR)的性质。我们发现在EAM过程中，肌肉浸润性T细胞的TCR Vbeta8.2、10和12被寡克隆性扩增。我们目前正在研究将这些Vbeta8.2、10和12全长插入到表达载体中的DNA疫苗预处理是否能抑制EAM的发展。我们还试图鉴定部分纯化的肌球蛋白制剂中的主要肌凝蛋白。为此，通过层析技术将部分纯化的肌球蛋白进一步纯化为纯化的肌球蛋白和C蛋白。用t-C蛋白免疫可引起严重的EAM，而用提纯的肌球蛋白免疫只引起轻微的肌肉病变。这一发现表明，C蛋白而不是肌球蛋白是主要的肌球蛋白生成抗原。

In order to know the pathogenesis of human polymyositis, experimetal autoimmune myositis (EAM) was induced in Lewis rats by immunization with partially purified myosin and the nature of T cell receptor (TCR) of EAM-inducing T cells was analyzed by CDR3 spectratyping. It was revealed that TCR Vbeta8.2, 10 and 12 of muscle-infiltrating T cells was oligoclonally expanded during the course of EAM.We are currently investigating whether pretreatment with DNA vaccines which are prepared by inserting full length of these Vbetas into the expression vector suppresses the development of EAM.We have also tried to identify the major myositogenic antigen in the partially purified myosin preparation. For this purpose, partially purified myosin was further purified by the chromatographic techniques into purified myosin and C-protein. Immunization with t C-protein induced severe EAM, whereas that with purified myosin produced only mild lesions in the muscle. This finding indicates that C-protein, but not myosin, is the major myositogenic antigen.