Immunologic Interaction between Infiltrating Eosinophils and T Lymphocytes in Murine Spontaneous Eosinophilic Myocarditis

Abstract

Background: Eosinophilic myocarditis often occurs spontaneously in DBA/2 mice. Relationships between infiltrating eosinophils (Eos), T lymphocytes and interleukin-5 (IL-5) in this disorder were investigated microscopically and immunohistochemically. Methods: Hearts from male DBA/2 mice were studied from 5 to 10 weeks of age. Anti-CD4 and anti-CD8 antibodies were used. Infiltrating Eos, white blood cells (WBC), and CD4+ and CD8+ T cells were counted. Interactions were assessed with multiple regression and forward stepwise regression tests. Additionally, IL-5 distribution in heart tissue was histologically observed with special reference to immunological findings. Results: Beginning at 5 weeks, several necrotic foci containing many damaged cardiocytes were seen in the epicardium of the right ventricle. Eos and lymphocytes were numerous within and around the necrotic foci. Eos were occasionally seen adjacent to degenerating cardiocytes. Three quarters of the mice exhibited such Eo-related myocardial damage. CD4+ lymphocytes were often seen infiltrating actively inflamed foci where Eos could also be observed. The lesional CD4+-to-CD8+ ratio (CD4/CD8) was 5.2 ± 3.3 at 6 weeks, 6.8 ± 3.7 at 7 weeks, and 1.5 ± 0.8 at 10 weeks of age. The lesional Eo/WBC ratio was directly proportional to the CD4/CD8 ratio (p < 0.05), and was also significantly related to lesional CD4+ T cell count (p < 0.05). IL-5 was also expressed in Eo-rich areas. Conclusions: In this mouse strain with susceptibility to eosinophilic myocarditis, Eo infiltration was related to increased lesional CD4+ cell count. We suspect that CD4+ T cells induce local eosinotaxis, mediated by IL-5, and participate in myocardiocyte injury via Eo induction.