title: [Direct analysis of HBV-specific CD8+ lymphocyte by tetrameric HLA-A2/core 18-27 complex in chronic Hepatitis B].
abstract: OBJECTIVE
  Hepatitis B virus(HBV) specific cytotoxic T lymphocyte (CTL) response is believed to play a major role in virus control and liver damage in chronic hepatitis B(CHB). We performed this study to evaluate whether HBV specific CTL could be visualized directly by tetrameric HLA-A2/core 18-27 complex(T c18-27) in the peripheral blood and liver of patients with CHB. On the basis of our results we clarified patients intrahepatic compartmentalization and correlation with HBV specific CTL and viral replication or liver damage.
  
  
  METHODS
  We stained peripheral blood mononuclear cells of 33 HLA-A2 + and 8 HLA-A2 patients with CHB with cytochrome conjugated anti-CD8 mAb and phycoerythrin conjugated T c18-27. Among these we analysed intrahepatic lymphocyte of 11 HLA-A2 + patients. We compared the frequency of T c18-27 specific CD8+ cells with serum HBV-DNA levels or alanine aminotransferase(ALT) levels.
  
  
  RESULTS
  The frequency of circulating T c18-27 specific CD8+ cell was higher(9-101 cells per 50,000 CD8+ cells) than background level in 14 among 33 patients. The frequency of intrahepatic T c18-27 specific CD8+ cells was 12-2100 cells per 50,000 CD8+ cells in 8 out of 11 patients whose liver was obtained This was 17.4-150 times higher than circulating T c18-27 specific CD8+ cells. The frequency of circulating T c18-27 specific CD8+ cells was increased in 10 out of 18 patients with serum HBV DNA level <0.5 pg/mL and ALT < 40 IU/L. It was increased in just 4 out of 15 patients with HBV DNA level > 800 pg/mL and ALT > 70 IU/L. The frequency of intrahepatic T c18-27 CTL tended to be lower in high levels of serum HBV DNA and was not correlated with liver inflammation.
  
  
  CONCLUSIONS
  This study proves that if HBV-specific CTLs are barely detectable in the peripheral blood of CHB, much more HBV-specific CTLs are in the liver and most HBV-specific CTLs are infiltrated in the liver. Also, in the presence of an effective HBV specific CD8 response the inhibition of viral replication can be independent of liver damage.
authors.affiliation: Department of Internal Medicine, National health insurance corporation Ilsan Hospital, Koyang, Korea. cklee33@nhimc.or.kr
authors.forename: Chun Kyon
authors.initials: CK
authors.lastname: Lee
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Suh
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Cho
authors.forename: Kwang Hyub
authors.initials: KH
authors.lastname: Han
authors.forename: Jae Bock
authors.initials: JB
authors.lastname: Chung
authors.forename: Chae Yoon
authors.initials: CY
authors.lastname: Chon
authors.forename: Young Myoung
authors.initials: YM
authors.lastname: Moon
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D015789:HLA-A2 Antigen / Q000032:analysis / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D015789:HLA-A2 Antigen; D014758:Viral Core Proteins