In situ expression of Granzyme B and Fas-ligand in the liver of viral hepatitis

Liver. 2002 Jun;22(3):198-204. doi: 10.1046/j.0106-9543.2002.00tes.x.

Abstract

Background/aims: The molecular mechanism involved in hepatocellular injury in viral hepatitis remains to be clarified.

Methods: We investigated the in situ expression of effector molecules of cytotoxic T lymphocytes such as Fas-ligand (Fas-L), perforin and Granzyme B (Gr-B) immunohistochemically in liver tissues from 20 patients with chronic hepatitis B (CHB) and C (CHC). The degree of cell infiltration was analysed semi-quantitatively and compared with the histological activity index (HAI). Fas-L was expressed in both CD4 and CD8 T-cells in the portal tract as well as in the parenchyma.

Results: Immunostaining of serial sections demonstrated that mononuclear cells at interface hepatitis and focal necrosis were mainly Fas-L positive CD8 T-cells. On the other hand, the expression of perforin or Gr-B was limited to a few mononuclear cells in the portal tract and parenchyma. Semi-quantitative analysis showed a positive correlation between HAI and the grade of infiltration of CD8 T-cells or Fas-L-positive cells, while the correlation was not apparent between HAI and the number of Gr-B positive cells. The expression of these molecules was not different between types of viruses.

Conclusions: These results suggest that Fas-L-positive CD8 T-cells play a major role in the pathogenesis of liver cell injury in chronic hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Count
  • Fas Ligand Protein
  • Female
  • Granzymes
  • Hepatitis B, Chronic / metabolism*
  • Hepatitis B, Chronic / pathology
  • Hepatitis C, Chronic / metabolism*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Immunoenzyme Techniques
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Serine Endopeptidases / metabolism*

Substances

  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases