A histological study on experimental autoimmune myocarditis with special reference to initiation of the disease and cardiac dendritic cells

Abstract

The precise mechanism of myosin-induced autoimmune myocarditis is unknown. The purpose of the present study was to define the immunohistological and ultrastructural characteristics of the infiltrating cells, especially in the initial phase of the myocarditis. It was demonstrated that OX6-positive dendritic cells first infiltrated the cardiocytes on day 13 after immunization. After day 17, OX6-positive cells, which possessed elongated irregular-shaped processes on the cell surface but contained few phago-lysosomes in the cytoplasm, were located at the margin of an inflammatory field and inserted their processes into the sarcoplasm of cardiocytes. The central portion of the inflammatory field was occupied by ED1-positive inflammatory macrophages, which were rich in phagosomes and which were in contact with degenerating cardiocytes. No evidence was obtained which suggested that lymphocytes directly injured the cardiocytes. These results demonstrated ultrastructural evidence that the type of infiltrating cell that first injures cardiocytes is the cardiac dendritic cell. Inflammatory macrophages thereafter serve as scavengers of degenerating cardiocytes.

Identification and Characterization of the Antigen Presenting Cell in Rat Autoimmune Myocarditis: Evidence of Bone Marrow Derivation and Non-requirement for MHC Class I Compatibility with Pathogenic T Cells

“…In areas of inflammation, cells bearing both ED1 and ED3 were seen. Our observations of the distribution of cells positive for these two antigens in autoimmune myocarditis agrees with that reported by Suzki [39] and mirrors descriptions of inflammation in other tissues, both autoimmune and injury induced [40,41]. The prevailing opinion is that these macrophage specific monoclonal antibodies ED1, ED2 and ED3 mark unique subsets of cells belonging to the monocyte/macrophage lineage.…”

Macrophage Inflammatory Protein-1α Relates to the Recruitment of Inflammatory Cells in Myosin-Induced Autoimmune Myocarditis in Rats

“…MIP-1␣, therefore, may be produced primarily by OX6-positive or ED2-positive cells before the onset of EAM. OX6 ϩ MIP-1␣ ϩ cells were seen approximately one half as frequently as ED2 ϩ MIP-1␣ ϩ cells in normal rats, as reported previously (Suzuki, 1995). Before the onset of EAM, the number of OX6 ϩ…”

“…OX6 mouse anti-rat Ia (MHC class II) antibody has been used to identify cardiac dendritic cells (DC) (Darden et al, 1987). Immunohistochemical and ultrastructural findings have suggested that OX6-positive cells present in the early phase of EAM were cardiac DC (Suzuki, 1995). In general, DC can activate immunologically naive T cells in the initiation of cell-mediated immune reaction (Steinman, 1991).…”

Fc Receptor–Mediated Inhibitory Effect of Immunoglobulin Therapy on Autoimmune Giant Cell Myocarditis

“…13 The primary antibodies (Serotec) used were as follows: OX62 antibody to recognize an integrin or integrin-like molecule present on DCs and ␥␦ T cells, 16 V65 antibody to specifically detect ␥␦ T cells, 17 OX6 antibody to recognize major histocompatibility complex (MHC) class II-expressing cells, including DCs, monocytes, and B lymphocytes, 13 ED1 antibody to detect inflammatory macrophages, 13 ED2 antibody to detect tissue macrophages, 13 W3/25 antibody to detect helper T lymphocytes and macrophages, 13 and OX8 antibody to detect cytotoxic/suppressor T lymphocytes. 13 W3/25 antibody is regarded as being directed against the rat homologue of CD4.…”

“…12 Accordingly, DCs appear to play an important role during the initial antigen-priming process of myocarditis. 11,13 Therefore, to clarify the FcR-mediated effects, we investigated the effects of immunoglobulin on autoimmune giant cell myocarditis with the analyses of immunologic behaviors of DCs and myocardial cytokines.…”