In situ expression of Granzyme B and Fas-ligand in the liver of viral hepatitis.
OBJECTIVE
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.
Ibuki
Naohisa
N
First Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
Yamamoto
Kazuhide
K
Yabushita
Kazuhisa
K
Okano
Nobuaki
N
Okamoto
Ryoichi
R
Shimada
Noriaki
N
Hakoda
Tomomi
T
Mizuno
Motowo
M
Higashi
Toshihiro
T
Tsuji
Takao
T
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D053222:Fas Ligand Protein; D005260:Female; D053804:Granzymes; D019694:Hepatitis B, Chronic / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases