A MOLECULAR BIOLOGICAL STUDY ON CARDIAC DENDRITIC CELL OF THE AUTOIMMUNE CARDIOMYOPATHY

心脏树突状细胞作为心肌组织中的一种新的基质细胞，在心脏的免疫应答中起着重要的作用。通过对大鼠实验性自身免疫性心肌炎（EAM）的几项研究，激发的树突状细胞显示了抗原特异性T细胞的活化和作为抗原呈递者的心脏炎症病变的启动。因此，本研究对自身免疫性心肌病的心脏树突状细胞进行了分子生物学研究，旨在阐明：1。树突状细胞在心肌炎和心肌病中的作用; 2.建立在体内和体外实验中工作良好的树突细胞的替代人工细胞的方法，和3.树突状细胞在慢性心力衰竭中的作用：首先，在人类心肌炎中，树突状细胞多出现在急性期。在持续性炎性病变中，细胞浸润程度与心肌炎的严重程度相对应。 ...更多信息 扩张型心肌病也有树突状细胞浸润，但其发生率远低于急性心肌炎。人心脏的细胞特征在表面抗原（阳性HLA-DR和阴性CD 68）方面与EAM非常相似，并且除了一个例外（像手套一样的细胞质加工）之外，还具有相同的形态。其次，为了筛选出对心肌肌球蛋白有特异性反应的T细胞克隆，我们尝试建立了一种杂交瘤细胞。杂交瘤被设计为在细胞表面上呈递MHC抗原。从EAM大鼠中分离淋巴细胞，并与来自BalB/c小鼠（M12.4.5）的B细胞淋巴瘤融合。因此，我们获得了细胞系MLEW。该杂交瘤能够介导具有心肌肌球蛋白的EAM淋巴细胞的特异性活化，并且当与^ Cr释放一起使用时<51>，它被记录为损伤心肌细胞。第三，实验证实了树突状细胞在慢性心力衰竭中的作用。在由自身免疫机制介导的心力衰竭中，T细胞强烈转化为TH 1，这有助于急性恶化。另一方面，为了缓解这种状态，T细胞从TH 1转移到TH 2。树突与这两条通路有着密切的关系。少

The cardiac dendritic cell, a new matrix cell in the myocardium, must play an important role in the immunoresponse of the heart. Through several studies on rat experimental autoimmune myocarditis, EAM, the provoked dendritic cell revealed an activation of antigen specific T cells and initiation of inflammatory lesions in the heart as an antigen presenter. Thus, the present study, a molecular biological study on cardiac dendritic cell of the autoimmune cardiomyopathy was designed to elucidate, 1. the role of the dendritic cell in the human myocarditis and cardiomyopathy, 2. a method to establish an alternative artificial cell of the dendritic cell that will work well in in vivo and in vitro experiments, and 3. the role of dendritic cell in the stage of chronic heart failure.Firstly, in human myocarditis, the dendritic cell frequently occurs in the acute phase. And, in persistent inflammatory lesion, the grade of the cell infiltrates corresponded well to the severity of the myocarditis. … More Dilated cardiomyopathy has also documented the dendritic infiltrates, but its occurrence has been far less in this disease than in acute myocarditis. Cellular characteristics of the human heart are very similar to ones of EAM in surface antigens (positive HLA-DR and negative CD68) and have also the same morphology except for one exception, cytoplasmic processing like a glove. Secondly, to identify a T cell clone that is specific respond with the cardiac myosin, we tried to establish a hybridoma cell. The hybridoma was designed to present MHC antigen on the cell surface. Lymphocytes were isolated from EAM rats, and were fused with B cell lymphoma originated from Balb/c mouse (M12.4.5). Consequently we obtained the cell line, MLEW.This hybridoma was able to mediate a specific activation of EAM lymphocyte with the cardiac myosin, and, when used with ^<51>Cr release it was documented to damage the cardiocyte. Thirdly, the dendritic cell's role in chronic heart failure was experimentally confirmed. In heart failure mediated by autoimmune mechanisms, T cells transform to TH1 intensively which contributes to acute worsening. On the other hand, for remission of this state, T cell shift from TH1 to TH2. The dendrites have a close relationship with both pathways. Less