Hepatitis C Virus (HCV)–Specific Immune Responses of Long‐Term Injection Drug Users Frequently Exposed to HCV
1Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, and 2Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, and 3Laboratory of Genomic Diversity, Science Applications International Cooperation–Frederick, National Cancer Institute at Frederick, Frederick, Maryland; 4University of California, San Francisco, and 5Blood Systems Research Institute, San Francisco, California; 6Center for the Study of Hepatitis C, Weill Medical College, Cornell University, and 7Center for the Study of Hepatitis C, The Rockefeller University, New York, New York
Background.
Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV‐specific immune responses in long‐term IDUs (duration, >10 years).
Methods.HCV‐specific T cell responses were assessed in proliferation, enzyme‐linked immunospot (ELISPOT), interferon (IFN)–γ secretion, and cytotoxicity assays, whereas HCV‐specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays.
Results.HCV‐specific T cell proliferation and IFN‐γ production were more common in nonviremic EIA‐positive IDUs (16 [94%] of 17 IDUs) than in viremic EIA‐positive IDUs (9 [45%] of 20 IDUs) (
). They were also noted in 16 (62%) of 26 nonviremic EIA‐negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA‐positive IDUs (
) and 0 of 24 nonviremic EIA‐negative IDUs. Nonviremic IDUs with nAbs were older (
) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV‐specific T cell responses.
Conclusion.The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses.
Received 6 July 2007; accepted 19 December 2007; electronically published 27 May 2008.
Cited by
Online publication date: 1-Aug-2009.
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Online publication date: 12-Jun-2009.
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Online publication date: 1-Feb-2009.
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Potential conflicts of interest: none reported.
Financial support: This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), and the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH; in whole or in part with federal funds from the National Cancer Institute, NIH (contract N01‐CO‐12400); and by the Public Health Service (grants AI050798 [to J.M.K.] and R01‐DA09532, R01‐DA13245, and R01‐DA16159 [to B.E.]) and the City and County of San Francisco Department of Public Health.
The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
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Present affiliations: First Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Ishikawa, Japan (for E.M.); Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany (for C.E.); First Department of Medicine, University Medical Centre Hamburg‐Eppendorf, Hamburg, Germany (for C.W.-N.); Division of Immunity and Infection, Institute of Biomedical Research, Medical School, University of Birmingham, Birmingham, United Kingdom (for J.A.M.).