Liver infiltrating T lymphocytes express interferon gamma and inducible nitric oxide synthase in chronic hepatitis C virus infection.
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 gamma (IFN-gamma) and IFN-gamma inducible type of nitric oxide synthase (iNOS) is increased in homogenised liver tissue of patients with chronic HCV infection.


OBJECTIVE
To determine the cellular origin of IFN-gamma and iNOS expression and to examine the hypothesis that T cell derived IFN-gamma 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-gamma and iNOS mRNA.


RESULTS
In chronic HCV infection, both IFN-gamma and iNOS gene expression were significantly increased. IFN-gamma 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-gamma and iNOS transcripts are elevated in chronic HCV infection. In contrast to the hypothesis, IFN-gamma expressing T cells do not induce iNOS in hepatocytes, but probably in T cells. T lymphocytes expressing IFN-gamma and/or iNOS have the potential to participate in autocrine and paracrine pathways that may contribute to the pathobiology of chronic hepatitis C.
Schweyer
S
S
Department of Pathology, Division of Pathology, Georg-August University, Göttingen, Germany.
Mihm
S
S
Radzun
H J
HJ
Hartmann
H
H
Fayyazi
A
A
D000328:Adult; D000368:Aged; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000235:genetics*; D008099:Liver / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II