Serial immunologic identification of lymphocyte subsets in murine coxsackievirus B3 myocarditis: different kinetics and significance of lymphocyte subsets in the heart and in peripheral blood.

Abstract

To elucidate possible immune mechanisms in the pathogenesis of myocarditis, we examined, by immunofluorescence techniques, the serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of C3H/He mice inoculated coxsackievirus B3 (experiment I). B cells were identified by staining with fluorescein isothiocyanate-labeled rabbit antimouse immunoglobulin. T cell subsets were demonstrated with rat anti-Thy 1.2, anti-Lyt 1, anti-Lyt 2, and anti-L3T4 monoclonal antibodies, respectively, plus fluorescein isothiocyanate-labeled antimouse immunoglobin. The percent of Thy 1.2+, Lyt 1+, and L3T4+ cells was decreased in the peripheral blood on days 3, 7, and 14. B cells were increased on day 3. In contrast, Thy 1.2+ (pan T) or Lyt 1+ cells appeared to occupy the major portion of the myocardium on days 7 and 14, when myocarditis was most severe, while B cells were sparse. For confirmation, serial immunohistologic studies (immunoperoxidase staining) of the hearts of C3H/He mice with coxsackievirus B3 myocarditis were performed (experiment II). Most of the stained cells in the heart were Thy 1.2, Lyt 1, and Lyt 2 positive on days 7 and 14. Thus, independent methods demonstrate that specific antigenic markers on lymphocytes at the site of inflammation in the acute stage of viral myocarditis differ from those on corresponding peripheral lymphocytes, and suggest the possible involvement of Thy 1.2+ (pan T) cells, mainly the Lyt 1+ and Lyt 2+ subsets (immature T cells), in the development of myocarditis in this preparation.