The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C

J Immunol 1997 Feb 1;158(3):1473-81
Nelson DR, Marousis CG, Davis GL, Rice CM, Wong J, Houghton M, Lau JY
Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville 32610, USA.

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.