Expression of tumour necrosis factor (TNF) receptor/ligand superfamily co-stimulatory molecules CD40, CD30L, CD27L, and OX40L in murine hearts with chronic ongoing myocarditis caused by coxsackie virus B3

T-cell-mediated myocardial damage has been shown to be involved in acute my ocarditis and dilated cardiomyopathy, It is necessary for T-cells to receiv e a co-stimulatory signal as well as the main signal through the T-cell rec eptor for antigen-specific T-cell activation to occur. To investigate the r oles of the co-stimulatory molecules CD40/CD40L, CD30/CD30L, CD27/CD27L, an d OX40/OX40L, which belong to the tumour necrosis factor (TNF) receptor/lig and superfamily, in the development of chronic ongoing myocarditis, the exp ression of CD40, CD30L, CD27L, and OX40L was analysed in the hearts of A/J mice with myocarditis induced by Coxsackie virus B3 (CVB3), The expression of CD40L, CD30, CD27, and OX40 was also examined on the infiltrating cells. Furthermore, the induction of CD40, CD30L, CD27L, and OX40L was evaluated on cultured cardiac myocytes treated,vith interferon (IFN)-gamma, CVB3-indu ced myocarditis resulted in the induction of CD40 and CD30L on the surface of cardiac myocytes, Induction of CD40 and CD30L on cardiac myocytes was co nfirmed by treatment with IFN-gamma, in vitro. CD27L and OX40L were express ed on cardiac myocytes in vivo and in vitro. The expression of CD27L and OX 40L on cardiac myocytes was increased, at least partly, by CVB3-induced myo carditis in vivo. Many infiltrating cells expressed CD27 and OX40, whereas much smaller numbers expressed CD40L and CD30. The induction of these molec ules, especially CD40 and CD30L, on cardiac myocytes strongly suggests that cardiac myocytes may co-stimulate T-cells and induce cytokine production b y T-cells and humoral immune responses. This may play an important role in the pathogenesis of the resulting myocardial damage. Copyright (C) 1999 Joh n Wiley & Sons, Ltd.