Analysis of T-cell receptor β-chain complementarity-determining region 3 motifs of infiltrating T cells in the inflammatory lesions from human myocarditis

心肌肌球蛋白诱导的大鼠实验性自身免疫性心肌炎（EAM）是人类巨细胞心肌炎的动物模型。急性暴发期后，EAM导致心肌炎后扩张型心肌病。本研究应用EAM技术探讨自身免疫性心肌损伤的发病机制。首先，我们分析了心肌中浸润的T细胞的T细胞受体互补决定区3（CDR 3）的结构。当用心肌肌球蛋白杆蛋白免疫大鼠时，心脏浸润T细胞的CDR 3基序受到限制。心肌肌球蛋白杆蛋白含有几个致心肌病的表位。当EAM诱导免疫与合成的mycarditogenic肽，心脏浸润T细胞寡克隆。对病变中t细胞的CDR 4基序的分析可能是自身免疫发病机制的标志物（Circulation Research 83：133-140，1998）。细胞因子在自身免疫性心肌损伤的发病机制中起重要作用。IL-12促进Th 0 T细胞转化为T细胞， ...更多信息 Th 1功能。IL-12 mRNA在EAM心肌中表达，观察IL-12对EAM的影响。IL-12的体内给药将EMA的自然病程转变为严重和持续的形式。因此，Th 1极性与EAM的发作、进展和持续有关（Circulation Research 82：1035-1042，1998）。柯萨奇病毒-腺病毒受体（CAR）是近年来发现的一种病毒，其基因已被克隆.该分子可能与心肌炎易感性有关。我们用EAM检测了CAR在大鼠心脏中的表达，CAR在新生大鼠心肌中有表达，而在成年大鼠心脏中未检测到。在EAM过程中，CAR的mRNA从免疫后18天开始在心肌上表达。免疫组织化学还显示CAR从第24天开始在心肌上表达。体外研究表明，CAR的心肌表达是由炎性细胞因子诱导的（Circulation Research 86：275-280，2000）。心肌炎患者病程的预测因素尚未确定。我们研究了急性心肌炎患者病程中各种参数的预测价值。我们收集了新泻县的心肌炎病例。分析了21例经组织学证实的心肌炎患者。13例急性期存活，其余均死亡。与存活组相比，死亡组血压较低，肺毛细血管楔压较高。死亡组血清可溶性Fas和Fas配体水平显著高于存活组。可溶性Fas和Fas配体可作为预测心肌炎患者预后的血清学标志物（Circulation 102：2829-2835，2000）。少

Cardiac myosin-induced rat experimental autoimmune myocarditis (EAM) is an animal model of human giant cell myocarditis. After the acute fulminant phase, EAM leads to post-myocarditis dilated cardiomyopathy. Pathogenesis of autoimmune myocardial injuries was investigated using EAM.Initially, we analyzed structure of the T-cell receptor complementarity determining region 3 (CDR3) of T-cells infiltrating in myocardium. When rats were immunized with cardiac myosin rod protein, CDR3 motif of the heart infiltrating T-cells were restricted. Cardiac myosin rod protein contains several myocarditogenic epitopes. When EAM was induced by immunization with a synthetic myocarditogenic peptide, heart infiltrating T-cells were oligoclonal. Analysis of CDR4 motif of t-cells in the lesion may be a marker for autoimmune pathogenesis (Circulation Research 83 : 133-140, 1998). Cytokines play important roles in the pathogenesis of autoimmune myocardial injuries. IL-12 promotes Th0 T-cells into T-cells with … More Th1 function. Messenger RNA of IL-12 was expressed in the myocardium in EAM.Effects of IL-12 were investigated. In vivo administration of IL-12 shifted the natural course of EMA to severe and persistent form. Thus, Th1 polarity related to the onset, progression and persistence of EAM (Circulation Research 82 : 1035-1042, 1998). Coxsakievirus and adenovirus receptor (CAR) has recently been found and its gene has been cloned. This molecule may be related to susceptibility of myocarditis. We investigated expression of CAR in the rat hearts with EAM.CAR was expressed on the neonatal myocardium, but it could not be detected on the adult rat heart. During the course of EAM, mRNA of CAR was expressed on the myocardium from 18 days after immunization. Immunohistochemistry also revealed expression of CAR on the myocardium from day 24. In vitro studies demonstrated that myocardial expression of CAR was induced by inflammatory cytokines (Circulation Research 86 : 275-280, 2000).Clinical manifestation of myocarditis vary from asymptomatic to fulminant and fatal form. The predictors of the course of the disease in patients with myocarditis have not yet been established. We examined the predictive values of various parameters in the disease course of patients with acute myocarditis. We collected human cases of myocarditis in Niigata prefecture. Twenty-one consecutive patients with histology-proven myocarditis were analyzed. Thirteen patients could survive acute phase and remainder were died. The fatal group had lower blood pressure and higher pulmonary capillary wedge pressure compared with the survival group. Serum levels of soluble Fas and Fas ligand were significantly higher in the fatal group than the survival group. Soluble Fas and Fas ligand would be serological marker to predict prognosis in patients with myocarditis (Circulation 102 : 2829-2835, 2000). Less