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Immuno-molecular-biological research on the pathogenesis of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

泰勒氏鼠脑脊髓炎病毒引起的脱髓鞘病发病机制的免疫分子生物学研究。

基本信息

批准号：
09670649
负责人：
INOUE Atsushi
金额：
$ 0.32万
依托单位：
Shinshu University
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-09670649/
关键词：
Theiler's virus demyelination cytokine Th1-Th2 balance Blood brain barrier T細胞エピトープペプチド

项目摘要

Intracerebral infection of susceptible mouse strains with Theiler's murine enephalomyelitis virus (TMEV) induces a chronic progressive demyelinating disease. This demyelinating disease (TMEV-IDD) is considered an infectious mouse model for MS because the disease displays similar histopathologic, genetic and clinical similarities to human MS.The breakdown of blood brain barrier is one of the important factors in the pathogenesis of demyelinating disease. We showed the fibrin deposition and increased permeability of blood brain barrier in the central nervous system correlated with the severity of TMEV-IDD (1). We examined the role of adhesion molecules of TMEV-IDD.We blocked the adhesion molecules such as ICAM-1 and LFA-1 by administration of these monoclonal antibodies (mAbs). These therapy suppressed the activity of virus specific CD4+ Th1 cells and clinical symptoms (2).We also examined the role of Th1-Th2 balance in TMEV-IDD using anti-IL-12 mAb or drugs such as phosphatidylserine, pentoxifylline that have the suppressed of the development of this disease both clinically and histologically (3-5). In the demyelination, antibodies against viral antigens play important roles. We studied the B cell epitopes of TMEV viral capsid protein and the effect of antibodies against these epitopes (6). Taking together, our data elucidated the certain mechanism of viral demyelination and showed the possibility of novel therapeutic approach in the clinical treatment of demyelinating disease such as human multiple sclerosis.

Theiler小鼠脑脊髓炎病毒（TMEV）的易感小鼠品系的脑内感染诱导慢性进行性脱髓鞘疾病。这种脱髓鞘疾病（TMEV-IDD）被认为是MS的感染性小鼠模型，因为该疾病显示出与人类MS相似的组织病理学，遗传学和临床相似性。血脑屏障的破坏是脱髓鞘疾病发病机制中的重要因素之一。我们发现中枢神经系统中的纤维蛋白沉积和血脑屏障通透性增加与TMEV-IDD的严重程度相关（1）。本研究通过应用这些单克隆抗体（mAb）阻断TMEV-IDD的粘附分子如ICAM-1和LFA-1。这些治疗抑制了病毒特异性CD 4 + Th 1细胞的活性和临床症状（2）。我们还使用抗IL-12 mAb或药物（如磷脂酰丝氨酸、戊茶碱）检测了Th 1-Th 2平衡在TMEV-IDD中的作用，这些药物在临床和组织学上抑制了这种疾病的发展（3-5）。在脱髓鞘过程中，抗病毒抗原的抗体起重要作用。我们研究了TMEV病毒衣壳蛋白的B细胞表位和针对这些表位的抗体的作用（6）。总之，我们的数据阐明了病毒性脱髓鞘的某些机制，并显示了在临床治疗脱髓鞘疾病如人类多发性硬化症的新治疗方法的可能性。