title: Hepatitis C virus (HCV)-specific immune responses of long-term injection drug users frequently exposed to HCV.
abstract: 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)-gamma 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-gamma 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) (P= .003). 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 (P= .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older (P= .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda 20892, USA.
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.forename: Christoph
authors.initials: C
authors.lastname: Eisenbach
authors.forename: Brian R
authors.initials: BR
authors.lastname: Edlin
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Newton
authors.forename: Sukanya
authors.initials: S
authors.lastname: Raghuraman
authors.forename: Christina
authors.initials: C
authors.lastname: Weiler-Normann
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Tobler
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Jane A
authors.initials: JA
authors.lastname: McKeating
authors.forename: Thomas R
authors.initials: TR
authors.lastname: O'Brien
authors.forename: Barbara
authors.initials: B
authors.lastname: Rehermann
mesh_terms: D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity*; D006526:Hepatitis C / Q000453:epidemiology / Q000276:immunology* / Q000635:transmission; D006801:Humans; D015994:Incidence; D007371:Interferon-gamma / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015819:Substance Abuse, Intravenous / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014481:United States / Q000453:epidemiology; D014764:Viral Proteins / Q000235:genetics; D014766:Viremia / Q000453:epidemiology
chemical_list: D016207:Cytokines; D014764:Viral Proteins; D007371:Interferon-gamma