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

• Published in: Hepatology research 2009-03, Vol.39 (3), p.256-265
• Main Authors: Doi, Hiroyoshi, Hiroishi, Kazumasa, Shimazaki, Tomoe, Eguchi, Junichi, Baba, Toshiyuki, Ito, Takayoshi, Matsumura, Takuya, Nozawa, Hisako, Morikawa, Kenichi, Ishii, Shigeaki, Hiraide, Ayako, Sakaki, Masashi, Imawari, Michio
• Format: Article
• Language: English
• Subjects: acute hepatitis C; CD8+ T-cell response; cytotoxic T lymphocyte; ELISpot assay; hepatitis C virus; interferon therapy
• ISSN: 1386-6346; 1872-034X
• DOI: 10.1111/j.1872-034X.2008.00459.x

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.