EXPERIMENTAL AUTOIMMUNE MYOCARDITIS: IMMUNOHISTOLOGICAL ANALYSIS WITH SPECIAL REFERENCE TO THE DENDRITIC CELL  MARKERS

Milosavljevic P.D. *, Milenkovic M. **, Colic M. *, Dimitrijevic M.**.
*Institute of Medical Research, Military Medical Academy, Crnotravska 17, 11002 Belgrade and **Department of Microbiology and Immunology, Faculty of Pharmacy, Belgrade, Yugoslavia

Introduction, Material & Methods

An experimental autoimmune myocarditis in genetically susceptible DA rats has been developed with the aim to investigate immunohistological changes in the course of the disease with special reference to the expression of the dendritic cell (DC) markers.
Male DA rats were immunized with porcine cardiac myosin in complete Freunds adjuvant (CFA). Animals were sacrificed at the different time points after the disease induction. Immunopathological changes of the heart tissue and phenotype of infiltrating cells were examined using immunoperoxidase and immunoalkaline phosphatase methods and monoclonal antibodies specific for rat MHC class II (OX6), CD80 and CD86 (costimulatory molecules) and OX62 (rat dendritic cells).

Results

In the hearts of control animals DC, predominantly localized in the interstitium, were OX6hi CD86lo CD80- OX62-. In the hearts of diseased animals the first changes were observed after one week, which were manifested as an increase in the expression of MHC class II (OX6) molecules. Rare perivascular DC, phenotypically OX6+ OX62+ CD86+ CD80lo appeared. On day 16, large cell infiltrates were observed. DC in the infiltrates were numerous and expressed strongly OX6, OX62 and CD86 markers, whereas the expression of CD80 was still lower. The number of OX62+ DC was lower then the numbers of other cells suggesting that CD80, CD86 as well as MHC class II molecules were also present on other cell types in the infiltrates, probably on macrophages. The number of DC in the interstitium was not significantly changed. Thirty two days after the disease induction, inflammatory infiltrates were reduced followed by the decrease in the DC number.
 
 

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Inflammatory infiltrates in heart muscle with massive
destruction of heart tissue 16 days after immunization


 


Conclusion

Our immunohistochemical analysis showed that  ED1+ MØ and  DC constitute a most significant populations of cells in inflammatory infiltrates which probably migrated from circulation rather than from the heart interstitium.
 
 


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