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

J Pathol. 1999 Aug;188(4):423-30. doi: 10.1002/(SICI)1096-9896(199908)188:4<423::AID-PATH373>3.0.CO;2-8.


T-cell-mediated myocardial damage has been shown to be involved in acute myocarditis and dilated cardiomyopathy. It is necessary for T-cells to receive a co-stimulatory signal as well as the main signal through the T-cell receptor for antigen-specific T-cell activation to occur. To investigate the roles of the co-stimulatory molecules CD40/CD40L, CD30/CD30L, CD27/CD27L, and OX40/OX40L, which belong to the tumour necrosis factor (TNF) receptor/ligand superfamily, in the development of chronic ongoing myocarditis, the expression 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 with interferon (IFN)-gamma. CVB3-induced myocarditis resulted in the induction of CD40 and CD30L on the surface of cardiac myocytes. Induction of CD40 and CD30L on cardiac myocytes was confirmed by treatment with IFN-gamma in vitro. CD27L and OX40L were expressed on cardiac myocytes in vivo and in vitro. The expression of CD27L and OX40L on cardiac myocytes was increased, at least partly, by CVB3-induced myocarditis in vivo. Many infiltrating cells expressed CD27 and OX40, whereas much smaller numbers expressed CD40L and CD30. The induction of these molecules, especially CD40 and CD30L, on cardiac myocytes strongly suggests that cardiac myocytes may co-stimulate T-cells and induce cytokine production by T-cells and humoral immune responses. This may play an important role in the pathogenesis of the resulting myocardial damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Antigens / metabolism
  • Cell Culture Techniques
  • Chronic Disease
  • Coxsackievirus Infections / immunology*
  • Enterovirus B, Human*
  • Immunoenzyme Techniques
  • Ki-1 Antigen / metabolism
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred A
  • Myocarditis / immunology*
  • Myocarditis / virology
  • Myocardium / immunology*
  • OX40 Ligand
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Tumor Necrosis Factors


  • CD40 Antigens
  • Ki-1 Antigen
  • Membrane Glycoproteins
  • OX40 Ligand
  • Receptors, Tumor Necrosis Factor
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factors