Cytomegalovirus induces class II expression in rat heart endothelial cells

An association between cytomegalovirus infection, cardiac allograft rejection, and atherosclerosis has been described. It has been suggested that cytomegalovirus induces major histocompatibility complex antigen expression in the graft and may trigger rejection. The induction of major histocompatibility complex antigens is thought to be mediated by interferon-gamma produced by activated T cells during the infection. To study whether cytomegalovirus infection induces major histocompatibility complex class II antigen expression in heart endothelium, cultured rat heart endothelial cells were infected with rat cytomegalovirus. The infection was shown by cytopathic effect and immunofluorescence using monoclonal cytomegalovirus-specific antibodies. Major histocompatibility complex class II antigen expression was analyzed before and during cytomegalovirus infection by two different methods, by a fluorescence-activated cell sorter and immunoperoxidase techniques using monoclonal antibodies. Uninfected endothelial cell cultures were treated with interferon-gamma and used as positive controls of class II induction. Induction of class II antigens was recorded in cytomegalovirus-infected endothelial cell cultures, and during the course of infection the class II expression increased toward the appearance of cytopathic effect. In uninfected cells, class II was induced by interferon-gamma, but this induction could be inhibited by adding antiinterferon-gamma antibody to the cultures. However, anti-interferon-gamma did not inhibit the induction of class II caused by cytomegalovirus. In conclusion, cytomegalovirus induced major histocompatibility complex class II antigen expression in rat heart endothelial cells in vitro. This induction of class II was independent of interferon-gamma and was caused by the virus itself. Direct induction of class II antigens by cytomegalovirus in heart endothelium may also be involved in rejection mechanisms in vivo.