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Development of the Specific Immunotherapy for Myocarditis, Dilated Cardiomyopathy(Chronic Myocarditis), and Takayasu Arteritis.

心肌炎、扩张型心肌病（慢性心肌炎）、大动脉炎的特异性免疫疗法的开发。

基本信息

批准号：
11557048
负责人：
SEKO Yoshinori
金额：
$ 8.64万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

1. Analysis of T-cell receptor(TCR)clonality of the heart infiltrating cells in myocarditis and dilated cardiomyopathy(DCM) : SSCP showed that TCR Vβ clonality was oligoclonal and about 40% of the total clones were identical among different three parts in the same heart and that about 40% of such clones also expanded in the peripheral blood. This indicates a possibility of identification of the antigen recognized by pathogenic T-cell clones playing a primary role in the development of the disease by collecting them from peripheral blood. 2. Analysis of costimulatory molecules playing an important role in the T-cell-mediated myocardial damage in acute and chronic myocarditis : (A)We analyzed TNF receptor/ligand superfamily costimulatory molecules in murine acute myocarditis, and found that CD30L, 4-1BBL, Fas were induced on cardiac myocytes and in vivo anti-4-1BBL or -FasL mAb administration significantly reduced the myocardial damage, indicating the critical role of 4-1BB/4-1BBL and Fa … More s/FasL pathways involved. (B)We found the induction of CD27L, CD30L, OX40L, and 4-1BBL on cardiac myocytes and expression of their counterpart by the infiltrating cells in patients with acute myocarditis and DCM, suggesting the role of these costimulatory molecules in the pathogenesis is of human myocarditis as well. 3. Analysis of TCR clonality of the arterial infiltrating cells in Takayasu Arteritis : (A)SSCP showed that TCR Vβ clonality was oligoclonal and most of the clones were identical between different two parts in the same arterial tissue, suggesting that limited clones infiltrated and recognized a certain antigen and caused vascular damage. (B)TCR γδ repertoire of the infiltrating cells was oligoclonal as was TCR αβ. 4. Analysis of costimulatory molecules in Takayasu Arteritis : It is strongly suggested that among TNF receptor/ligand superfamily costimulatory molecules, especially 4-1BB/4-1BBL and Fas/FasL pathways play an important role in the vascular damage involved in Takayasu Arteritis. Less

1. 心肌炎和扩张型心肌病（DCM）心脏浸润细胞的t细胞受体（TCR）克隆分析：SSCP显示TCR Vβ克隆为寡克隆，在同一心脏的不同三个部位中约有40%的克隆是相同的，约40%的克隆在外周血中也有扩增。这表明有可能通过从外周血中收集病原性t细胞克隆识别的抗原，这些抗原在疾病的发展中起主要作用。2. 急慢性心肌炎中t细胞介导心肌损伤的共刺激分子分析(A)我们分析了小鼠急性心肌炎中TNF受体/配体超家族共刺激分子，发现CD30L、4-1BBL、Fas可诱导心肌细胞，体内抗4-1BBL或-FasL单抗可显著减轻心肌损伤，表明4-1BB/4-1BBL和Fa…更多s/FasL通路参与其中。(B)在急性心肌炎和DCM患者中，我们发现CD27L、CD30L、OX40L和4-1BBL在心肌细胞上的诱导作用，并通过浸润细胞表达相应的CD27L、CD30L、OX40L和4-1BBL，提示这些共刺激分子在人类心肌炎的发病机制中也有作用。3. 高松动脉炎动脉浸润细胞的TCR克隆分析：(A)SSCP显示TCR Vβ克隆为寡克隆，且同一动脉组织中不同部位的TCR Vβ克隆大部分相同，提示有限克隆浸润并识别某种抗原，造成血管损伤。(B)浸润细胞的TCR γδ库为寡克隆，TCR αβ库为寡克隆。4. 高松动脉炎共刺激分子分析：强烈提示TNF受体/配体超家族共刺激分子，特别是4-1BB/4-1BBL和Fas/FasL通路在高松动脉炎血管损伤中起重要作用。少