Differential expression of perforin and granzyme B in the liver of patients with chronic hepatitis C.
T lymphocytes have been reported to be the predominant inflammatory cells in the liver of patients with chronic hepatitis C. On activation, CD8+ T lymphocytes can exert their cytolytic activity by releasing their granule components, notably perforin and granzyme B. The aim of the present study was to assess whether the granule cytolytic pathway was used by liver-infiltrating CD8+ T lymphocytes. Immunostaining for perforin and granzyme B was performed in 25 patients with chronic hepatitis C, according to the disease activity and their virologic status. Cells stained for perforin and for granzyme B represented 0.15% and 0.10% of the total liver-infiltrating CD8+ T lymphocytes, respectively. Perforin was expressed mainly by activated CD8+ T lymphocytes located in liver lobules. In contrast, granzyme B was expressed mainly by activated CD8+ T lymphocytes located in interface hepatitis and portal tracts. The results were similar in the different groups of patients, whatever the disease activity. In conclusion, this is the first study showing a differential expression of granule components of CD8+ T lymphocytes in the same tissue in vivo. Perforin and granzyme B may be differently expressed by liver-infiltrating CD8+ T lymphocytes, according to their localization in the different specific compartments of the liver, in patients with chronic hepatitis C.
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D005260:Female; D053804:Granzymes; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; 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; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism* / Q000473:pathology
D015703:Antigens, CD; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012367:RNA, Viral; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases