Polarity of helper T cell subsets represents disease nature and clinical course of experimental autoimmune myocarditis in rats

Abstract

SUMMARY The mechanisms of progression, remission and relapse of myocarditis remain unclear. To clarify these mechanisms, we focused on T helper-1 (Th1)/T helper-2 (Th2) subsets balance of peripheral lymphocytes and serum cytokine levels during disease progression in rats with experimental autoimmune myocarditis (EAM). Lewis rats were immunized with cardiac myosin on day 0. Blood samples were collected on days 0, 7, 15, 18, 21, 28, 35, 42, 49 and 56 following immunization. We examined percentages of interferon (IFN)-γ and/or interleukin (IL)-4 producing cells in stimulated peripheral CD4-positive lymphocytes using flow cytometry analysis. Serum IFN-γ, IL-2, IL-6 and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA). The percentage of Th1/Th2 subsets in EAM on days 0, 15, 28 and 56 were 2·5 ± 0·5/0·5 ± 0·1%, 19·4 ± 3·2/1·6 ± 0·3%, 2·0 ± 0·5/22·1 ± 5·7% and 3·0 ± 0·4/1·7 ± 0·3%, respectively. Serum levels of Th1 cytokines, IFN-γ and IL-2 significantly increased in the acute phase (from day 15–18) and immediately decreased in the early recovery phase. On the other hand, serum levels of Th2 cytokine, IL-10 significantly increased in the early recovery phase (from day 24–30). These results suggest that induction of acute myocarditis might be associated with systemic Th1 dominance, while recovery is related to systemic Th2 polarity. Thus, analysis of Th1/Th2 balance in peripheral T cells may be useful in disease monitoring in patients with myocarditis and postmyocarditic dilated cardiomyopathy.