The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection

Anthony J. Freeman, Yong Pan, Charles E. Harvey, Jeffrey J. Post, Matthew G. Law, Peter A. White, William D. Rawlinson, Andrew R. Lloyd, George Marinos, Rosemary A. Ffrench

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61 Citations (Scopus)

Abstract

Background/Aims: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. Methods: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. Results: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P < 0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P = 0.004). Hepatic lobular infiltration by CD8+T cells correlated weakly with serum alanine aminotransferase levels (r = 0.42, P = 0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. Conclusions: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.

Original languageEnglish
Pages (from-to)349-356
Number of pages8
JournalJournal of Hepatology
Volume38
Issue number3
DOIs
Publication statusPublished - 1 Mar 2003
Externally publishedYes

Keywords

  • CD8
  • Chronic hepatitis
  • Cytotoxicity
  • Immunity
  • Viral persistence

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