CYTOMEGALOVIRUS INDUCES CLASS-II EXPRESSION IN RAT-HEART ENDOTHELIAL-CELLS

An association between cytomegalovirus infection, cardiac allograft re jection, 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 m ajor histocompatibility complex antigens is thought to be mediated by interferon-gamma produced by activated T cells during the infection. T o study whether cytomegalovirus infection induces major histocompatibi lity complex class II antigen expression in heart endothelium, culture d rat heart endothelial cells were infected with rat cytomegalovirus. The infection was shown by cytopathic effect and immunofluorescence us ing monoclonal cytomegalovirus-specific antibodies. Major histocompati bility complex class II antigen expression was analyzed before and dur ing cytomegalovirus infection by two different methods, by a fluoresce nce-activated cell sorter and by immunoperoxidase techniques using mon oclonal antibodies. Uninfected endothelial cell cultures were treated with interferon-gamma and used as positive controls of class II induct ion. Induction of class II antigens was recorded in cytomegalovirus-in fected endothelial cell cultures, and during the course of infection t he class II expression increased toward the appearance of cytopathic e ffect. In uninfected cells, class II was induced by interferon-gamma, but this induction could be inhibited by adding antiinterferon-gamma a ntibody to the cultures. However, anti-interferon-gamma did not inhibi t the induction of class II caused by cytomegalovirus. In conclusion, cytomegalovirus induced major histocompatibility complex class II anti gen 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 cytomegaloviru s in heart endothelium may also be involved in rejection mechanisms in vivo.