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

Andrea L. Cox, Timothy Mosbruger, Georg M. Lauer, Drew Pardoll, David L. Thomas, Stuart C. Ray

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)104-112
Number of pages9
JournalHepatology
Volume42
Issue number1
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Hepatology

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