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Liver infiltrating T lymphocytes express interferon γ and inducible nitric oxide synthase in chronic hepatitis C virus infection
  1. S Schweyera,
  2. S Mihmb,
  3. H J Radzuna,
  4. H Hartmannb,
  5. A Fayyazia
  1. aDepartment of Pathology, Division of Pathology, Georg-August University, Göttingen, Germany, bDepartment of Internal Medicine, Division of Gastroenterology and Endocrinology
  1. Dr S Schweyer, Universitätsklinikum Göttingen, Abteilung Pathologie, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany.

Abstract

BACKGROUND Pathogenesis of hepatitis C virus (HCV) associated liver injury is thought to be due to the host antiviral immune response. Using a quantitative, competitive RT-PCR technique, we recently showed that expression of interferon γ (IFN-γ) and IFN-γ inducible type of nitric oxide synthase (iNOS) is increased in homogenised liver tissue of patients with chronic HCV infection.

AIMS To determine the cellular origin of IFN-γ and iNOS expression and to examine the hypothesis that T cell derived IFN-γ secretion induces iNOS in hepatocytes in chronic HCV infection.

METHODS By applying a non-radioactive in situ hybridisation method combined with indirect immunofluorescence, 33 liver biopsy specimens from patients with chronic HCV infection were studied for cellular expression of IFN-γ and iNOS mRNA.

RESULTS In chronic HCV infection, both IFN-γ and iNOS gene expression were significantly increased. IFN-γ and iNOS mRNA were observed in CD3+ lymphocytes infiltrating portal tracts and hepatic lobules, but not in hepatocytes.

CONCLUSIONS Results are consistent with previous reports that IFN-γ and iNOS transcripts are elevated in chronic HCV infection. In contrast to the hypothesis, IFN-γ expressing T cells do not induce iNOS in hepatocytes, but probably in T cells. T lymphocytes expressing IFN-γ and/or iNOS have the potential to participate in autocrine and paracrine pathways that may contribute to the pathobiology of chronic hepatitis C.

  • hepatitis C
  • interferon type II
  • nitric oxide synthase
  • in situ hybridisation
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Footnotes

  • Abbreviations used in this paper:
    ALT
    alanine aminotransferase
    DIH
    drug induced hepatitis
    HbsAg
    hepatitis B surface antigen
    HBV
    hepatitis B virus
    HCV
    hepatitis C virus
    IFN-γ
    interferon γ
    iNOS
    inducible nitric oxide synthase
    ISH
    in situ hybridisation
    PBC
    primary biliary cirrhosis
    Th1
    T helper 1

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