title: Fate and function of hepatitis-C-virus-specific T-cells during peginterferon-alpha2b therapy for acute hepatitis C.
abstract: BACKGROUND
  Strong hepatitis C virus (HCV)-specific T-cell responses are associated with spontaneous clearance of acute hepatitis C. However, recent studies described a decline in HCV-specific CD8+ T-cells during interferon treatment, suggesting that the success of acute HCV therapy might be independent of adaptive immunity.
  
  
  METHODS
  T-cell responses of eight human leukocyte antigen (HLA)-A2-positive, acutely infected patients treated with peginterferon-alpha2b were studied by ELISPOT and proliferation assays and flow cytometry analysis using HCV-specific tetramers.
  
  
  RESULTS
  HCV-specific T-cells predominately declined during therapy. However, diverse patterns of CD4+ and CD8+ T-cell kinetics were observed. In patients with sustained virological response chemokine receptor 3 (CXCR-3) expression of HCV-specific CD8+ T-cells was upregulated, indicating homing to the liver. Low levels of T-cells remained detectable throughout treatment and follow up. In contrast, T-cells of a relapse patient did not upregulate CXCR-3 but displayed a higher staining for annexin-V, followed by a complete loss of peripheral virus-specific CD8+ T-cells by week 12.
  
  
  CONCLUSIONS
  Kinetics of HCV-specific T-cell responses are heterogeneous in interferon-treated patients with acute hepatitis C. The decline of T-cells might be a consequence of both apoptosis and homing. The balance between cell death and regulation of chemokine receptors might lead to different long-term outcomes.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Wiegand
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.forename: Nuray
authors.initials: N
authors.lastname: Aslan
authors.forename: Verena
authors.initials: V
authors.lastname: Schlaphoff
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.forename: Anne
authors.initials: A
authors.lastname: Kubitschke
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.forename: Ayse
authors.initials: A
authors.lastname: Ciner
authors.forename: Elmar
authors.initials: E
authors.lastname: Jaeckel
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D017304:Annexin A5 / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use*; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015789:HLA-A2 Antigen / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D008969:Molecular Sequence Data; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism; D011994:Recombinant Proteins; D013045:Species Specificity; D016896:Treatment Outcome
chemical_list: D017304:Annexin A5; D000998:Antiviral Agents; C515187:CXCR3 protein, human; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b