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刘易斯大鼠，诱导实验性自身免疫性肌炎（EAM），并通过CDR 3谱分析EAM诱导T细胞的T细胞受体（TCR）性质。结果显示，在EAM过程中，肌肉浸润T细胞的TCR V β 8.2、10和12寡克隆扩增。我们目前正在研究通过将这些V β的全长插入表达载体制备的DNA疫苗的预处理是否抑制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成丝抗原。为此目的，部分纯化的肌球蛋白进一步纯化的层析技术，以纯化肌球蛋白和C-蛋白。免疫与t C-蛋白诱导严重的EAM，而纯化的肌球蛋白只产生轻微的病变的肌肉。这一发现表明，C蛋白，而不是肌球蛋白，是主要的肌生蛋白抗原。

项目成果

G.Kim et al.: "CDR3 size spectratyping and sequencing of spectratype-derived T cell receptor of spinal cord T cells in autoimmune encephalomyelitis"J.Immunol. 160. 509-513 (1998)

G.Kim 等人：“自身免疫性脑脊髓炎中脊髓 T 细胞的光谱类型衍生 T 细胞受体的 CDR3 大小光谱分型和测序”J.Immunol。

G.Kim, N.Tanuma, T.Kojima, K.Kohyama, Y.Suzuki, Y.Kawazoe & Y.Matsumoto: "CDR3 size spectratyping and sequencing of spectratype-derived T cell receptor of spinal cord T cells in autoimmune encephalomyelitis."J. Immunol.. 160. 509-513 (1998)

G.Kim、N.Tanuma、T.Kojima、K.Kohyama、Y.Suzuki、Y.Kawazoe

Y.Matsumoto, Y.Kohyama, Y.Aikawa, T.Shin, Y.Kawazoe, Y.Suzuki, N.Tanuma: "Role of natural killer cells and TCRUPSILONdelta T cells in acute autoimmune encephalomyelitis." Eur.J.Immunol.28. 1681-1688 (1998)

Y.Matsumoto、Y.Kohyama、Y.Aikawa、T.Shin、Y.Kawazoe、Y.Suzuki、N.Tanuma：“自然杀伤细胞和 TCRUPSILONdelta T 细胞在急性自身免疫性脑脊髓炎中的作用。”

T.Kohji et al.: "Interaction between apoptotic cells and reactive brain cells in the central nervous system of rats with autoimmune encephalomyelitis" J.Neuroimmunol.(in press). (1998)

T.Kohji 等人：“自身免疫性脑脊髓炎大鼠中枢神经系统中凋亡细胞与反应性脑细胞之间的相互作用”J.Neuroimmunol.（出版中）。

T.Kojima et al.: "Myosin-induced autoimmune polymyositis in the rats." J.Neurol.Sci.151. 141-147 (1997)

T.Kojima 等人：“大鼠中肌球蛋白诱导的自身免疫性多发性肌炎。”