Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

Hepatology. 2005 Jul;42(1):104-12. doi: 10.1002/hep.20749.


We comprehensively studied the cellular immune response during acute human hepatitis C virus (HCV) infection by monthly prospective sampling of persons at high risk of infection. In 19 of 23 subjects, interferon-gamma-secreting T cells specific for 1 or more peptides spanning the entire HCV polyprotein were detected 1 to 3 months after infection. The median time to development of interferon gamma responses to HCV peptides was 33 days (range, 29-50 days), and these responses peaked between 180 and 360 days. Nineteen subjects had sufficient follow-up to determine outcome, with 15 (79%) developing persistent viremia and 4 (21%) clearing viremia spontaneously. Of those with progression to chronic infection and detectable T cell responses, all lost recognition of one or more antigens recognized during acute infection, and the median reduction in the magnitude of responses was 85%. Most significantly, despite ongoing viremia, those who had persistent infection did not develop new epitope specificities after the first 6 months of infection. In conclusion, in most individuals, the CD8+ T cell responses generated early in HCV infection decline in peripheral blood and are not replaced with new responses. Supplementary material for this article can be found on the HEPATOLOGY website (

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Hepatitis C / immunology*
  • Humans
  • Male
  • Prospective Studies