Controlled study of autoimmunization against liver in inbred rat strains1

SUMMARY By prolonged immunization of an inbred rat strain with isologous liver homogenate in Freund's complete adjuvant a low grade autoimmune 'cholangitis ' with periductular fibrosis has been demonstrated. The lesion could be transferred to isogeneic animals by serial spleen cell in-jections and was associated with mild but variable delayed skin sensitivity to a supernatant fraction of the liver homogenate. It is thought to be due to a combined cellular and antibody-mediated immune response, directed against bile duct constituents. Pulmonary (peribronchial) lesions have also been described in the same animals and are considered to be of similar origin and to represent a cross reaction with tissue of similar embryological (entodermal) origin. This appears to be the first description of periductular hepatic fibrosis clearly resulting from an autoimmune reaction and may provide a model for further study of rather similar histological reactions known to occur in man. In previous reports (Maclaurin and Humm, 1968 and 1969) it has been demonstrated that a low-grade portal triaditis can be induced in rats by repeated injections of homologous liver homogenate in complete Freund's adjuvant, and that this live