Nature Medicine
6, 578 - 582 (2000)
doi:10.1038/75063
Cellular immune responses persist and humoral responses decrease two
decades after recovery from a single-source outbreak of hepatitis CAkinobu Takaki1, 6, Manfred Wiese2, Geert Maertens3, Erik Depla3, Ulrike Seifert1, Anke Liebetrau2, Jeffery L. Miller4, Michael P. Manns1
& Barbara Rehermann1, 51
Department of Gastroenterology and Hepatology, Medizinische
Hochschule Hannover, Carl-Neuberg-Str. 1, 30625
Hannover, Germany
2
II. Klinik für Innere Medizin, Städtisches
Klinikum St. Georg, Delitzscher Str. 141, 04129
Leipzig, Germany
3
Hepatitits Program, Innogenetics, Industriepark
Zwijnaarde 7, Box 4, 9052 Gent, Belgium
4
Laboratory of Chemical Biology, National Institutes
of Health, 10 Center Drive, Rm 9B16, Bethesda
, Maryland 20892, USA
5
Liver Diseases Section, NIDDK, National Institutes
of Health, 10 Center Drive, Rm 9B16, Bethesda
, Maryland 20892, USA
6
present address: The First Department of Internal Medicine,
Okayama University Medical School, 2-5-1 Shikata-cho,
Okayama, 700-8558 Japan
Correspondence should be addressed to Barbara Rehermann Rehermann@nih.govAs 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)- -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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