MURINE HEPATITIS CAUSED BY LYMPHOCYTIC CHORIOMENINGITIS VIRUS .1. THEHEPATIC-LESIONS

BACKGROUND: The hepatitis that occurs after adult mice are infected wi th lymphocytic choriomeningitis (LCM) virus is immune mediated, althou gh the details of the pathogenetic mechanisms are largely unknown. To better understand the sequence of events leading to alterations typica l for hepatitides with immunopathogenesis, livers of immunocompetent m ice infected with LCM virus were examined. EXPERIMENTAL DESIGN: Virus replication and histopathology in the livers and concentrations of liv er enzymes in the sera of C57BL/6 mice were followed from day 3 throug h day 14 after intraperitoneal infection with 10(6) mouse infectious u nits of LCM virus. Histologic, histochemical, immunohistologic, and in situ hybridization methods were used to determine the cells involved in the inflammatory process. RESULTS: Infectious virus rose to 10(9) m ouse infectious units/g of liver by day 7 and declined thereafter. Vir al RNA and antigen were localized in foci of hepatocytes and in Kupffe r and endothelial cells of the sinusoids. Disseminated spotty necroses , steatosis, a marked sinusoidal reaction, and lobular and (later) per iportal mononuclear infiltrates were observed. In the infiltrates, T c ells predominated followed by macrophages and NK cells; the number of B and plasma cells rose moderately. Among T lymphocytes the CD8(+) cel ls increased preferentially, and the CD4/CD8 ratio changed from 1.7 to 0.3. Other features were major histocompatibility complex antigen exp ression on hepatocytes, enhanced immunocytochemical evidence of fibron ectin and ICAM-1 in sinusoids, and deposition of immunoglobulin, compl ement, and fibrinoid. Changed,activities of liver enzymes and bilirubi n levels paralleled the pathologic alterations. CONCLUSIONS: Although CD8(+) T cells seem to be central in the pathogenesis of LCM hepatitis , probably more than one immunopathologic mechanism is operative.