Immunohistochemical characterization of infiltrating mononuclea cells in the rat heart with experimental autoimmune giant cell myocarditis

Abstract

SUMMARY The pathogenesis of giant cell myocarditis remains unclear. Subsets of inflammatory infiltrating cells may reflect the pathogenesis and etiology of the disease. Therefore, we examined subsets of infiltrating mononuclear cells in the heart of the rat with experimental giant cell myocarditis. Lewis rats were immunized with cardiac myosin in Freund's complete adjuvant (FCA). Severe myocarditis characterized by congestive heart failure and multinucleated giant cells were elicited. The lesions were composed of predominant mononuclear cells, polymorphonuclcar neutrophils and fragments of degenerated myocardial fibres. The subsets of infiltrating mononuclear cells were investigated using MoAbs against rat CD4+ T cell (W3/25), CD8 + T cell (CX8), B cell (OX33) and macrophage(OX42). By serial examination, bound immunoglobulin could only be found on degenerated myocardial fibres. In this model, most infiltrating mononuclear cells were composed of macrophages and CD4 + T cells. The frequencies of macrophages and CD4+ T cells were 73·7% and 13·8%, respectively. CD8+ T cells were scarce and B cells were rare in the lesions. The frequencies of CD8 + T cells and B cells were 4·5% and 0·4%, respectively. The dominance of macrophages and CD4+ T cells was the constant finding among the sites of the lesions and throughout the course of the disease. These characteristic subsets of infiltrating cells were in contrast to those of murine viral myocarditis which were mainly composed of natural killer (NK) cells and CD8+ T cells. Clarifying the subsets of infiltrating cells in myocarditis may contribute to differential diagnosis of myocarditis between viral and autoimmune types. From this study, the pathogenesis of experimental autoimmune giant cell myocarditis seemed to be closely related to CD4+ T cells and macrophages.