Interstitial fibrin-fibronectin deposition with T cell infiltrates precedes fibrosis in murine viral myocarditis

This study was carried out to investigate interstitial fibrin and fibronectin deposition and subsequent myocardial connective tissue abnormalities in BALB/c-nu/+ (euthymic and normal T cell function) and BALB/c-nu/nu (athymic and T cell-deficient) mice. Both types of mice were inoculated with encephalomyocarditis virus and sacrificed periodically. Sections of the hearts were stained with haematoxylin-eosin, trichrome, lymphocyte subsets, silver impregnation, and fibrin or fibronectin. In addition, myocardial collagen concentration was measured. Interstitial fibrin and fibronectin appeared in parallel with inflammatory T lymphocytes and myocardial necrosis in the BALB/c-nu/+ mice. The changes increased until 14 days, subsequently decreasing with time. Interstitial fibrosis and abnormal reticulin fibres were absent until 7 days postinfection, and then increased with time until 60 days. In BALB/c-nu/nu mice, in contrast, although myocardial necrosis and fibrin-fibronectin deposition associated with immature T lymphocytes were evident on days 7 and 14, subsequent myocardial fibrosis and reticulin fibre abnormalities were minimal on days 30 and 60. In BALB/c-nu/+ mice, myocardial collagen concentration increased on day 30, but it did not in BALB/c-nu/nu mice. Thus, interstitial fibrin-fibronectin deposition resulting from virus-induced and T lymphocyte-mediated myocyte necrosis precedes the subsequent development of interstitial fibrosis and abnormal reticulin architectures in this model of murine myocarditis.