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Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C

Nature Medicine volume 6, pages 578–582 (2000)Cite this article

Abstract

As acute hepatitis C virus (HCV) infection is clinically inapparent in most cases, the immunologic correlates of recovery are not well defined. The cellular immune response is thought to contribute to the elimination of HCV-infected cells1 and a strong HCV-specific T-helper-cell (Th) response is associated with recovery from acute hepatitis C (ref. 2). However, diagnosis of resolved hepatitis C is based at present on the detection of HCV-specific antibodies and the absence of detectable HCV RNA, and detailed comparison of the humoral and cellular immune response has been hampered by the fact that patient cohorts as well as HCV strains are usually heterogeneous and that clinical data from acute-phase and long-term follow-up after infection generally are not available. We studied a cohort of women accidentally exposed to the same HCV strain of known sequence3 and found that circulating HCV-specific antibodies were undetectable in many patients 18–20 years after recovery, whereas HCV-specific helper and cytotoxic T-cell responses with an interferon (IFN)-γ-producing (Tc1) phenotype persisted. The data indicate these HCV-specific CD4+ and CD8+ T cells are biomarkers for a prior HCV exposure and recovery. Because of undetectable antibodies against HCV, the incidence of self-limited HCV infections and recovery may be underestimated in the general population.

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Figure 1: Humoral immune response.
Figure 2: CD4+ T-cell response.
Figure 3: CD8+ T-cell response.

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Acknowledgements

We thank all patients who donated blood for this study; S. Bigl and L. Müller (Landesuntersuchungsanstalt, Chemnitz, Germany) for providing patient samples; T. Forsthuber (Case Western Reserve University, Cleveland, Ohio), for advice regarding the elispot technique; N. Kezmic, R. Hummes and B. Nentwig for technical assistance; and T. J. Liang and J. Hoofnagle (National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health) for discussion. This study was supported by grants Re1017/2-2 (Deutsche Forschungsgemeinschaft, Bonn, Germany) and 1297 (01KI 9659/5 Pathogenesis of HCV infection), Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (BMBF), Bonn, Germany, to B.R. and by grant IWT970259 (Eureka Project EU180 Hepatitits C) from the Flemish Government to Innogenetics.

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  1. Akinobu Takaki

    Present address: The First Department of Internal Medicine, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, Hannover, 30625 , Germany

    Akinobu Takaki, Ulrike Seifert, Michael P. Manns & Barbara Rehermann

  2. II. Klinik für Innere Medizin, Städtisches Klinikum St. Georg, Delitzscher Str. 141, Leipzig, 04129 , Germany

    Manfred Wiese & Anke Liebetrau

  3. Hepatitits Program, Innogenetics, Industriepark Zwijnaarde 7, Box 4, Gent, 9052, Belgium

    Geert Maertens & Erik Depla

  4. Laboratory of Chemical Biology, National Institutes of Health, 10 Center Drive, Rm 9B16, Bethesda , 20892, Maryland, USA

    Jeffery L. Miller

  5. Liver Diseases Section, NIDDK, National Institutes of Health, 10 Center Drive, Rm 9B16, Bethesda , 20892, Maryland, USA

    Barbara Rehermann

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Correspondence to Barbara Rehermann.

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Takaki, A., Wiese, M., Maertens, G. et al. Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C. Nat Med 6, 578–582 (2000). https://doi.org/10.1038/75063

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