Murine hepatitis caused by lymphocytic choriomeningitis virus. I. The hepatic lesions.
BACKGROUND
The hepatitis that occurs after adult mice are infected with lymphocytic choriomeningitis (LCM) virus is immune mediated, although the details of the pathogenetic mechanisms are largely unknown. To better understand the sequence of events leading to alterations typical for hepatitides with immunopathogenesis, livers of immunocompetent mice infected with LCM virus were examined.


METHODS
Virus replication and histopathology in the livers and concentrations of liver enzymes in the sera of C57BL/6 mice were followed from day 3 through day 14 after intraperitoneal infection with 10(6) mouse infectious units 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) mouse infectious units/g of liver by day 7 and declined thereafter. Viral RNA and antigen were localized in foci of hepatocytes and in Kupffer and endothelial cells of the sinusoids. Disseminated spotty necroses, steatosis, a marked sinusoidal reaction, and lobular and (later) periportal mononuclear infiltrates were observed. In the infiltrates, T cells predominated followed by macrophages and NK cells; the number of B and plasma cells rose moderately. Among T lymphocytes the CD8+ cells increased preferentially, and the CD4/CD8 ratio changed from 1.7 to 0.3. Other features were major histocompatibility complex antigen expression on hepatocytes, enhanced immunocytochemical evidence of fibronectin and ICAM-1 in sinusoids, and deposition of immunoglobulin, complement, and fibrinoid. Changed activities of liver enzymes and bilirubin 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.
Löhler
J
J
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Hamburg, Germany.
Gossmann
J
J
Kratzberg
T
T
Lehmann-Grube
F
F
D000818:Animals; D005260:Female; D015870:Gene Expression; D006524:Hepatitis, Viral, Animal / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006649:Histocompatibility Antigens / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology*; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D014779:Virus Replication / Q000502:physiology
D006649:Histocompatibility Antigens