Interferon gamma production by peripheral blood lymphocytes to hepatitis C virus core protein in chronic hepatitis C infection

✍ Scribed by Kazuo Iwata; Takaji Wakita; Akihiko Okumura; Kentaro Yoshioka; Masahiro Takayanagi; Jack R. Wands; Shinichi Kakumu

• Book ID: 102854190
• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 890 KB
• Volume: 22
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840220407

✦ Synopsis

Evidence suggests that cellular immunity to hepatitis C virus (HCV) core protein may be important in the pathogenesis of viral infection. Therefore, interferon gamma (IFNy) production by peripheral blood mononuclear cells (PBMC) derived from patients with chronic HCV infection (genotype lb) was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein derived from a patient with genotype lb. To identify the immunodominant epitopes, IFN-y production in responders was also assessed with a panel of nine synthetic peptides that covered the entire core region. It was found that mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein; asymptomatic HCV carriers demonstrated a lower response rate (14%, P < .05). More important, individuals who had received IFN-a treatment and went into clinical and virological remission had a higher response rate (75%, P < .05) compared with those with ongoing hepatitis whose treatment failed (31%). Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141 to 160 was recognized in 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141 to 160. Thus, IFN-y production of the mononuclear cell response appeared to be HLA DR restricted, and the responding cells were identified as CD4' T cells.