The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C.
Cellular immune responses, particularly those mediated by CD8+ CTL, may be important in the pathogenesis and control of hepatitis C virus (HCV) infection. To define the role of HCV-specific CTL in chronic hepatitis C, HCV-specific CTL activity in liver and peripheral blood was assessed in 35 patients with chronic HCV infection and 5 non-HCV controls. HCV-specific CTL activity of expanded CD8+ cells was evaluated against autologous lymphoblastoid cells transduced with recombinant vaccinia virus vectors expressing HCV genotype 1a Ags. CTL activity was detected in unprimed bulk-expanded CD8+ cells derived from the liver in 16 of the 35 patients, but not in peripheral circulation. Three patients infected with non-type 1 HCV were found to have HCV-specific CTL activity against HCV type 1a epitopes, all directed toward HCV core region. Compared with patients without detectable HCV-specific CTL activity based on our assay, those exhibiting CTL activity had lower levels of viremia (p < 0.01 for both branched DNA version 1.0 and 2.0 assays) and more active disease, as reflected by a higher histologic activity index (p = 0.006) and serum alanine aminotransferase levels (p = 0.03). It is concluded that 1) with nonspecific stimulation, HCV-specific CTL activity is found more commonly in the liver than in peripheral circulation, suggesting a tissue-specific localization with HCV-specific CTL and/or its precursors; 2) cross-genotype CTL activity exists, especially toward HCV core, which is relatively conserved across genotypes; and 3) patients with intrahepatic HCV-specific CTL activity had lower levels of viremia and more active liver disease.
Nelson
D R
DR
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville 32610, USA.
Marousis
C G
CG
Davis
G L
GL
Rice
C M
CM
Wong
J
J
Houghton
M
M
Lau
J Y
JY
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D003602:Cytotoxicity, Immunologic; D005260:Female; D005814:Genes, Viral; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000473:pathology; D018936:Hepatitis C Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018936:Hepatitis C Antigens; D015395:Histocompatibility Antigens Class I; D012367:RNA, Viral