Perforin and granzyme B lytic protein expression during chronic viral and autoimmune hepatitis.
BACKGROUND
Cytotoxic T lymphocytes and Kupffer cells are essential components of the immune response during liver diseases. Recent studies have highlighted the role of cytotoxic T lymphocytes using Fas and its ligand in induced hepatocyte death during acute and chronic hepatitis.


METHODS
In the present work, the main purpose was to investigate perforin and granzyme B expression in liver biopsies of patients with chronic hepatitis (10 HBV, 14 HCV and 10 autoimmune hepatitis) using immunohistochemistry. The liver biopsies of two normal individuals were also studied in the same conditions.


RESULTS
Few intrahepatic T lymphocytes expressed perforin and granzyme B, while a large number of Kupffer cells were positive for both proteins in all the patients tested. The co-localization of perforin and granzyme B, and CD3 or CD68 antigens was visualized, respectively, in T cells and Kupffer cells, using confocal microscopy. In situ hybridization assays confirmed that perforin and granzyme B mRNAs were present in the liver during chronic hepatitis. The results were similar among the three groups of patients and whatever the activity of the disease. Perforin and granzyme B expression was lacking in liver samples from normal individuals.


CONCLUSIONS
These data suggest a minor role for the T cell-mediated perforin/granzyme B death pathway, and a putative role for Kuppfer cells via lytic protein release, during chronic hepatitis.
Tordjmann
T
T
Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier, Bondy, France.
Soulie
A
A
Guettier
C
C
Schmidt
M
M
Berthou
C
C
Beaugrand
M
M
Sasportes
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D005260:Female; D053804:Granzymes; D019694:Hepatitis B, Chronic / Q000378:metabolism* / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology; D019693:Hepatitis, Autoimmune / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D053804:Granzymes; D008562:Membrane Glycoproteins; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D012697:Serine Endopeptidases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C509213:GZMB protein, human