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

1.心肌炎和扩张型心肌病（DCM）心脏浸润细胞T细胞受体（TCR）克隆性分析：SSCP显示，TCR Vβ克隆性为寡克隆性，约40%的克隆在同一心脏不同部位之间是相同的，约40%的克隆在外周血中也有扩增。这表明，通过从外周血中收集在疾病发展中起主要作用的致病性T细胞克隆，有可能鉴定出它们所识别的抗原。2.在急慢性心肌炎T细胞介导的心肌损伤中起重要作用的共刺激分子的分析：（A）我们分析了小鼠急性心肌炎中的TNF受体/配体超家族共刺激分子，发现在心肌细胞上诱导了CD 30 L、4-1BBL、Fas，并且体内抗4-1BBL或-FasL mAb施用显著降低了心肌损伤，表明4-1BB/4-1BBL和Fa的关键作用 ...更多信息 s/FasL通路。(B)We发现在急性心肌炎和扩张型心肌病患者心肌细胞上诱导CD 27 L、CD 30 L、OX 40 L和4-1BBL，并通过浸润细胞表达其对应物，提示这些共刺激分子在人类心肌炎发病机制中也起作用。3.多发性大动脉炎动脉浸润细胞TCR V β克隆性分析：（A）SSCP显示，TCR Vβ克隆性为寡克隆性，同一动脉组织不同部位的TCR V β克隆大多数相同，提示有限的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库是寡克隆的，TCR αβ也是寡克隆的。4.共刺激分子在大动脉炎中的作用分析：在TNF受体/配体超家族共刺激分子中，特别是4-1BB/4-1BBL和Fas/FasL通路在大动脉炎的血管损伤中起重要作用。少

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