期刊
GASTROENTEROLOGY
卷 132, 期 2, 页码 654-666出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2006.11.044
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资金
- MRC [G0400802] Funding Source: UKRI
- Medical Research Council [G0400802, G9818340B] Funding Source: researchfish
- Medical Research Council [G0400802, G0801976] Funding Source: Medline
- NCI NIH HHS [P30 CA016520] Funding Source: Medline
- NCRR NIH HHS [K12 RR17625, M01-RR00040] Funding Source: Medline
- NIAAA NIH HHS [AA12849] Funding Source: Medline
- NIAID NIH HHS [AI47519] Funding Source: Medline
- NIDDK NIH HHS [P30DK50306, T32 DK07066] Funding Source: Medline
Background & Aims: Acute hepatitis C virus (HCV) infection becomes chronic in the majority of patients. Although HCV-specific CD4 T-cell response is associated with HCV clearance, less is known about virus-specific CD8 T-cell or neutralizing antibody (nAb) responses and the role of CD4 help in their induction during acute infection. Methods: HCV-specific CD4, CD8, and HCV pseudoparticle (HCVpp) nAb responses were monitored in acutely HCV-infected patients to define their relative contributions to viral clearance. Results: Our results show that the outcome of acute hepatitis C is associated with a functional hierarchy in HCV-specific CD4 T-cell response and the scope of virus-specific, total T-cell interferon-gamma response. HCV-specific CD8 T-cell response was readily detectable in acutely HCV-infected patients regardless of virologic outcome or virus-specific CD4 T-cell response. In contrast, HCVpp-specific nAbs were readily detected in patients with chronic evolution and impaired virus-specific CD4 T-cell response but not in patients who cleared infection with robust virus-specific CD4 T-cell response. Conclusions: The outcome of acute hepatitis C is associated with efficient virus-specific CD4 T-cell response(s) without which HCV-specific CD8 T-cell and heterologous nAb responses may develop but fail to clear viremia. Furthermore, HCV-specific nAb responses may not be induced despite robust virus-specific CD4 T-cell response.
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