title: Loss of virus-specific T-cell responses in HCV exposed uninfected injection drug users with drug rehabilitation.
abstract: BACKGROUND
  Hepatitis C virus (HCV)-specific T lymphocyte responses have been demonstrated in peripheral blood from injection drug users (IDUs) persistently HCV antibody and RNA negative despite high-risk behavior. We have termed these apparently HCV resistant cases "Exposed Uninfecteds" (EUs), and have studied the evolution of T-cell responses to determine if they are protective in nature.
  
  
  METHODS
  Twenty-one EU cases were studied using a questionnaire to ascertain injecting behavior details. Peripheral blood mononuclear cells were isolated from whole blood and an interferon-gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT) assay used to detect T-cell responses to a panel of HCV proteins. EU cases were subdivided by injecting drug patterns into (1) cases in rehabilitation who stopped injecting, (2) prisoners (infrequent/noninjectors), and (3) cases who continued to inject.
  
  
  RESULTS
  EUs continuing to inject had significantly stronger (P < .01) and more frequent (P < .05) HCV-specific IFN-γ ELISPOT responses than controls or noninjecting EUs. EUs in rehabilitation lost their T-cell responses during follow-up, while those continuing to inject maintained them.
  
  
  CONCLUSIONS
  HCV-specific T-cell responses in EU cases wane within months of cessation of injection drug use. Maintenance of these T-cell responses appears to be dependent on continuing HCV exposure through injection drug use.
authors.affiliation: Hepatology Research Group, Peninsula College of Medicine and Dentistry, Universities of Plymouth & Exeter, Plymouth, UK.
authors.forename: Prem H
authors.initials: PH
authors.lastname: Thurairajah
authors.forename: Doha
authors.initials: D
authors.lastname: Hegazy
authors.forename: Andrew
authors.initials: A
authors.lastname: Demaine
authors.forename: Edward R
authors.initials: ER
authors.lastname: Kaminski
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Cramp
mesh_terms: D000328:Adult; D015331:Cohort Studies; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008875:Middle Aged; D016485:Needle Sharing; D011329:Prisoners; D012307:Risk Factors; D015819:Substance Abuse, Intravenous / Q000097:blood / Q000534:rehabilitation* / Q000821:virology*; D011795:Surveys and Questionnaires; D013601:T-Lymphocytes / Q000276:immunology*; D006113:United Kingdom; D055815:Young Adult
chemical_list: D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D007371:Interferon-gamma