Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia

Biliary atresia (BA) is an inflammatory cholangiopathy of infancy. A proposed mechanism regarding the pathogenesis of BA is that of a virus-induced, immune-mediated injury to bile ducts. The rotavirus (RRV)-induced murine model of BA was utilized to determine the hepatic inflammatory response related to ductal obstruction and if the immune response recapitulated human BA. One week after infection, there was a significant increase in liver CD4(+) T cells producing IFN-γ and in macrophages producing TNF-α. The intrahepatic pattern of inflammation evolved rapidly from an initial predominant CD4(+) Thl cellular response to a subsequent influx of activated rnacrophages producing TNF-α and NOS. This immune response persisted despite viral clearance and was representative of the hepatic immune profile present in human BA. Utilization of the murine model of BA yielded mechanistic data that can provide much needed insight into the role played by different arms of the immune system related to the pathogenesis of human BA. © 2005 Elsevier Inc. All rights reserved.