Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance

A. Folgori, E. Spada, M. Pezzanera, L. Ruggeri, A. Mele, A. R. Garbuglia, M. P. Perrone, P. Del Porto, E. Piccolella, R. Cortese, A. Nicosia, A. Vitelli

Research output: Contribution to journalArticle

Abstract

Background and aims: Cellular mediated immunity (CMI) is thought to play a key role in resolution of primary hepatitis C virus (HCV) infection. However, CD4+ and CD8+ T cell responses are also generated during acute infection in individuals who become chronic, suggesting that they developed a defective CMI. The aim of this study was to verify if and when such immune dysfunction is established by measuring the breadth, magnitude, function, and duration of CMI in a large cohort of subjects during the natural course of acute HCV infection. Methods: CMI was comprehensively studied by prospective sampling of 31 HCV acutely infected subjects enrolled at the onset of infection and followed for a median period of one year. Results: Our results indicated that while at the onset of acute HCV infection a measurable CMI with effector function was detected in the majority of subjects, after approximately six months less than 10% of chronically infected individuals displayed significant CMI compared with 70% of subjects who cleared the virus. We showed that progressive disappearance of HCV specific T cells from the peripheral blood of chronic patients was due to an impaired ability to proliferate that could be rescued in vitro by concomitant exposure to interleukin 2 and the antigen. Conclusion: Our data provide evidence of strong and multispecific T cell responses with a sustained ability to proliferate in response to antigen stimulation as reliable pharmacodynamic measures of a protective CMI during acute infection, and suggest that early impairment of proliferation may contribute to loss of T cell response and chronic HCV persistence.

Original languageEnglish
Pages (from-to)1012-1019
Number of pages8
JournalGut
Volume55
Issue number7
DOIs
Publication statusPublished - Jul 2006

ASJC Scopus subject areas

  • Gastroenterology

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    Folgori, A., Spada, E., Pezzanera, M., Ruggeri, L., Mele, A., Garbuglia, A. R., Perrone, M. P., Del Porto, P., Piccolella, E., Cortese, R., Nicosia, A., & Vitelli, A. (2006). Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance. Gut, 55(7), 1012-1019. https://doi.org/10.1136/gut.2005.080077