title: Decades after recovery from hepatitis B and HBsAg clearance the CD8+ T cell response against HBV core is nearly undetectable.
abstract: OBJECTIVE
  CD8(+) T cells are an essential component of a successful immune response against hepatitis B virus (HBV). Patients who spontaneously clear HBsAg after acute HBV infection have a strong CD8(+) T cell immune response, predominantly directed against the HBV core protein (HBcAg). However, the fate and phenotype of HBcAg-specific CD8(+) T cells after immune control are unclear.
  
  
  METHODS
  The CD8(+) T cell immune response against HBV core was determined in 65 patients with chronic HBV infection, 16 patients after recovery from acute HBV infection, and four patients with acute HBV infection utilizing overlapping peptides and HLA class I/peptide-multimers.
  
  
  RESULTS
  Patients who had cleared HBsAg >30 years ago had significantly weaker CD8(+) T cell responses after antigen-specific expansion compared to patients who had cleared the virus <10 years ago and patients with HBeAg negative chronic infection and low viral load (<2000 IU/ml; p<0.01). Also directly ex vivo, patients who had cleared the HBsAg >30 years ago had less HBV-specific CD8(+) T cells compared to patients with HBeAg negative chronic infection (p=0.0025). In patients with acute HBV infection, the frequency of HBc-specific CD8(+) T cells continued to decline after clearance of HBV-DNA and HBsAg even at a time when ALT levels had already normalized (p=0.0313).
  
  
  CONCLUSIONS
  The frequency of HBcAg-specific CD8(+) T cells continuously declines after HBsAg clearance. In line with clinical observations, this suggests that humoral and not CD8(+) T cell immune responses mainly contribute to prevention of HBV reactivation decades after HBsAg clearance.
authors: Institute of Virology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany; Department of Gastroenterology, University Hospital Essen, Essen, Germany.
authors: Helenie
authors: H
authors: Kefalakes
authors: Department of Gastroenterology, University Hospital Essen, Essen, Germany.
authors: Christoph
authors: C
authors: Jochum
authors: Department of Gastroenterology, University Hospital Essen, Essen, Germany.
authors: Gudrun
authors: G
authors: Hilgard
authors: Department of Gastroenterology, University Hospital Essen, Essen, Germany.
authors: Alisan
authors: A
authors: Kahraman
authors: Department of Neurosurgery, University Hospital Essen, Essen, Germany.
authors: Anna Margarethe
authors: AM
authors: Bohrer
authors: Department of Neurosurgery, University Hospital Essen, Essen, Germany.
authors: Nicolai
authors: N
authors: El Hindy
authors: Institute for Transfusion Medicine, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.
authors: Falko Markus
authors: FM
authors: Heinemann
authors: Institute of Virology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.
authors: Jens
authors: J
authors: Verheyen
authors: Department of Gastroenterology, University Hospital Essen, Essen, Germany.
authors: Guido
authors: G
authors: Gerken
authors: Institute of Virology, Technical University of Munich, Munich, Germany.
authors: Michael
authors: M
authors: Roggendorf
authors: Institute of Virology, University of Duisburg-Essen, University Hospital Essen, Essen, Germany; Institute of Virology, Heinrich-Heine-University, University Hospital, Düsseldorf, Germany. Electronic address: joerg.timm@med.uni-duesseldorf.de.
authors: Joerg
authors: J
authors: Timm
mesh_terms: D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D008099:Liver / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens
keywords: Anti-HBs; CD8(+) T cell response; HBV core; HBcAg; HBsAg