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BACKGROUND & AIMS: Virus-specific CD4+ T cells play a major role in hepatitis C virus (HCV) infection. Viral clearance is associated with vigorous and multispecific CD4+ T cell responses, while chronic infection has been shown to be associated with weak or absent T cell responses. Most of these studies, however, have used functional assays to analyse virus-specific CD4+ T cell responses. Therefore, the important question, of whether virus-specific CD4+ T cells are completely absent or primarily impaired in specific effector functions during chronic infection, has yet to be analysed in detail. METHODS: To address this issue, a novel assay, where CD4+ T cell frequencies can be determined by de novo CD154 (CD40 ligand) expression in response to HCV antigens, was used in a cohort of chronically infected HCV patients and patients who spontaneously resolved HCV infection. These responses were compared to functional assays, such as the IFN-gamma ELISpot and flow cytometry-based proliferative assays. RESULTS: Our results reveal that using the CD154 assay, virus-specific CD4+ T cells are readily detectable during chronic HCV infection albeit at a lower frequency when compared to patients who spontaneously resolved the infection. Importantly, no CD4+ T cell responses were detectable from these patients when using functional assays. Finally, these cell populations were enriched in the intrahepatic compartment. CONCLUSIONS: Our findings suggest that HCV-specific CD4+ T cell responses are readily detectable in chronic HCV infection and enriched in the infected liver.

Original publication




Journal article


J Hepatol

Publication Date





800 - 811


Adult, Aged, Amino Acid Sequence, Antibodies, Blocking, Biopsy, CD4-Positive T-Lymphocytes, CD40 Ligand, Cell Division, Cells, Cultured, Convalescence, Female, Flow Cytometry, Hepatitis C Antigens, Hepatitis C, Chronic, Histocompatibility Antigens Class II, Humans, Immunomagnetic Separation, Interferon-gamma, Liver, Male, Middle Aged, Molecular Sequence Data, Recombinant Proteins, Up-Regulation