Analysis of experimental autoimmune myositis and its immunotherapy

实验性自身免疫性肌炎及其免疫治疗分析

• 批准号: 09670682
• 负责人: KOJIMA Takashi
• 金额: $ 1.79万
• 依托单位: Tokyo Metropolitan Institute for Neuroscience
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670682/
• 关键词: polymyositis; myositogenic T cells; T cell receptor; CDR3 spectrayping; DNA vaccine

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.

为了了解人类多发性肌炎的发病机制，通过用部分纯化的肌球蛋白免疫Lewis大鼠来诱导实验性自身免疫性肌炎（EAM），并通过CDR3谱分型分析诱导EAM的T细胞的T细胞受体（TCR）的性质。结果表明，肌肉浸润 T 细胞的 TCR Vbeta8.2、10 和 12 在 EAM 过程中寡克隆扩增。我们目前正在研究是否用通过将这些 Vbeta 全长插入表达载体而制备的 DNA 疫苗进行预处理抑制EAM的发展。我们还尝试鉴定部分纯化的肌球蛋白制剂中的主要肌生成抗原。为此，部分纯化的肌球蛋白通过色谱技术进一步纯化为纯化的肌球蛋白和C蛋白。 t C 蛋白免疫诱导了严重的 EAM，而纯化肌球蛋白仅在肌肉中产生轻微损伤。这一发现表明，C 蛋白而非肌球蛋白是主要的肌生成抗原。

项目成果

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T.Kojima 等人：“大鼠中肌球蛋白诱导的自身免疫性多发性肌炎。”