Seko Y, Ishiyama S, Nishikawa T, Kasajima T, Hiroe M, Kagawa N, Osada K, Suzuki S, Yagita H, Okumura K
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
J Clin Invest. 1995 Aug;96(2):1035-41. doi: 10.1172/JCI118089.
Prolonged myocardial cell damage initiated by acute myocarditis is thought to be one of the most important etiology of dilated cardiomyopathy. To investigate the immunological mechanisms involved in the pathogenesis of dilated cardiomyopathy, we analyzed the phenotypes of infiltrating cells and examined the expression of perforin in infiltrating cells in the hearts of patients with dilated cardiomyopathy as well as acute myocarditis. We also examined the expression of HLA and intercellular adhesion molecule-1 (ICAM-1) in myocardial tissue of these patients. Furthermore, to evaluate the antigen specificity of infiltrating T cells and persistence of viral genomes in the myocardial tissue, we analyzed the expression of T cell receptor (TCR) V alpha and V beta genes as well as enterovirus genomes by PCR. We found infiltration of perforin-expressing killer cells and enhanced expression of HLA class I and ICAM-1 in the myocardial tissue. We also found that the repertoires of TCR V alpha as well as V beta gene transcripts were restricted, indicating that a specific antigen in the hearts was targeted. Because no enterovirus genomes were detected in all patients, it is strongly suggested that a cell-mediated autoimmune mechanism triggered by virus infection may play a critical role in the pathogenesis of dilated cardiomyopathy. However, we could not exclude the possibility that viruses other than enteroviruses could be pathogenic in these patients.
急性心肌炎引发的心肌细胞长期损伤被认为是扩张型心肌病最重要的病因之一。为了研究扩张型心肌病发病机制中涉及的免疫机制，我们分析了浸润细胞的表型，并检测了扩张型心肌病患者以及急性心肌炎患者心脏中浸润细胞中穿孔素的表达。我们还检测了这些患者心肌组织中 HLA 和细胞间黏附分子 -1（ICAM -1）的表达。此外，为了评估浸润 T 细胞的抗原特异性以及心肌组织中病毒基因组的持续性，我们通过 PCR 分析了 T 细胞受体（TCR）Vα和 Vβ基因以及肠道病毒基因组的表达。我们发现心肌组织中有表达穿孔素的杀伤细胞浸润，且 HLA I 类分子和 ICAM -1 的表达增强。我们还发现 TCR Vα以及 Vβ基因转录本的库受到限制，表明心脏中的一种特定抗原是靶点。由于在所有患者中均未检测到肠道病毒基因组，强烈提示病毒感染引发的细胞介导的自身免疫机制可能在扩张型心肌病的发病机制中起关键作用。然而，我们不能排除除肠道病毒外的其他病毒在这些患者中具有致病性的可能性。
