CYTOMEGALOVIRUS-INFECTION IS ASSOCIATED WITH INCREASED INFLAMMATION AND SEVERE BILE-DUCT DAMAGE IN RAT-LIVER ALLOGRAFTS

It has been suggested that cytomegalovirus (CMV) infection is involved in allograft rejection, In liver transplantation, it has been suggest ed that CMV is associated with the development of vanishing bile duct syndrome (VBDS), and persistent CMV has been found in liver grafts tha t develop chronic rejection, In this experimental study, the effect of rat CMV (RCMV) infection on intragraft changes was investigated in a rat model of acute liver allograft rejection, Liver transplantations w ere performed in a rat strain combination of PVG (RT1(c)) --> BN (RT1( n)). No immunosuppression was given, One group of animals was infected with RCMV Maastricht Strain (10(5) plaque-forming units, intraperiton eally), and another group was left uninfected, The grafts were examine d histologically after the rats were killed on postoperative days 7 th rough 9 at the early phase and days 20 through 30 at the late phase of rejection. Immunohistochemical studies were performed to demonstrate the immunological activation markers major histocompatibility complex class II and interleukin 2 receptors, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and their l igands, RCMV infection was demonstrated from the grafts by culture and direct antigen detection, In liver allografts undergoing acute reject ion, CMV significantly increased portal inflammation and caused more s evere bile duct damage than in the uninfected grafts, CMV was also lin ked to the induction of VCAM-1 in the endothelial cells. The ongoing i nfection was found to vary over time in the different structures of th e liver grafts, including the vascular endothelium and bile ducts, Our results support an association between CMV infection and the immunolo gical mechanisms of rejection, as well as the role of CMV in the devel opment of bile duct damage in liver allografts.