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Magnitude of CD8+ T-cell responses against hepatitis C virus and severity of hepatitis do not necessarily determine outcomes in acute hepatitis C virus infection
Authors:Hiroyoshi Doi  Kazumasa Hiroishi  Tomoe Shimazaki  Junichi Eguchi  Toshiyuki Baba  Takayoshi Ito  Takuya Matsumura  Hisako Nozawa  Kenichi Morikawa  Shigeaki Ishii  Ayako Hiraide  Masashi Sakaki  Michio Imawari
Institution:Department of Gastroenterology, Showa University School of Medicine, Tokyo, Japan
Abstract:Aim:  We investigated the relationship between the magnitude of comprehensive hepatitis C virus (HCV)-specific CD8+ T-cell responses and the clinical course of acute HCV infection.
Methods:  Six consecutive patients with acute HCV infection were studied. Analysis of HCV-specific CD8+ T-cell responses was performed using an interferon-γ-based enzyme-linked immunospot assay using peripheral CD8+ T-cells, monocytes and 297 20-mer synthetic peptides overlapping by 10 residues and spanning the entire HCV sequence of genotype 1b.
Results:  Five patients presented detectable HCV-specific CD8+ T-cell responses against a single and different peptide, whereas 1 patient showed responses against three different peptides. Neither the magnitude of HCV-specific CD8+ T-cell responses nor the severity of hepatitis predicts the outcome of acute hepatitis. The maximum number of HCV-specific CD8+ T-cells correlated with maximum serum alanine aminotransferase level during the course ( r  = 0.841, P  = 0.036).
Conclusions:  HCV-specific CD8+ T-cell responses were detectable in all 6 patients with acute HCV infection, and 6 novel HCV-specific CTL epitopes were identified. Acute HCV infection can resolve with detectable HCV-specific CD8+ T-cell responses, but without development of antibody against HCV.
Keywords:acute hepatitis C  CD8+ T-cell response  cytotoxic T lymphocyte  ELISpot assay  hepatitis C virus  interferon therapy
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