1. Early impairment of hepatitis C virus specific T cell proliferation during acute infection leads to failure of viral clearance.
- Author
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Folgori A, Spada E, Pezzanera M, Ruggeri L, Mele A, Garbuglia AR, Perrone MP, Del Porto P, Piccolella E, Cortese R, Nicosia A, and Vitelli A
- Subjects
- Acute Disease, Adult, Antigens, Viral immunology, CD4-Positive T-Lymphocytes immunology, Case-Control Studies, Cell Proliferation, Chi-Square Distribution, Cohort Studies, Female, Hepacivirus genetics, Humans, Interferon-gamma immunology, Interleukin-1 immunology, Male, Middle Aged, RNA, Viral blood, Reverse Transcriptase Polymerase Chain Reaction, Hepacivirus immunology, Hepatitis C immunology, T-Lymphocytes immunology
- 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.
- Published
- 2006
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