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

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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