title: Dynamic changes of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and natural killer T (NKT) cells in patients with acute hepatitis B infection.
abstract: BACKGROUND
  The goal of this study is to observe changes in HBcAg-specific cytotoxic T lymphocytes (CTLs), natural killer (NK) and natural killer T (NKT) cells from peripheral blood and to relate such changes on viral clearance and liver injury in patients with acute hepatitis B (AHB).
  
  
  METHODS
  Dynamic profiles on the frequency of HLA-A0201-restricted HBcAg18-27 pentamer complex (MHC-Pentamer)-specific CTLs and lymphocyte subsets in AHB patients were analyzed in addition to liver function tests, HBV serological markers, and HBV DNA levels. ELISPOT was used to detect interferon-gamma (INF-γ) secretion in specific CTLs stimulated with known T cell epitope peptides associated with HBV surface protein, polymerase, and core protein.
  
  
  RESULTS
  HBV-specific CTL frequencies in AHB patients were much higher than in patients with chronic hepatitis B (CHB) (p<0.05). HBeAg and HBV DNA disappeared earlier in AHB patients with a high frequency of HBV-specific CTLs compared with those with a low frequency of HBV-specific CTLs (p=0.001 and 0.024, respectively). INF-γ spots of effector cells stimulated by Pol575-583, Env348-357, or Core18-27 epitope peptides were significantly greater in AHB patients than in CHB patients (p<0.01). CD3+CD8+ T cell numbers in AHB patients was more than observed in the healthy control group from the first to the fourth week after admission (p=0.008 and 0.01, respectively); the number of CD3+CD8+ T cells and frequency of HBcAg18-27-specific CTLs in AHB patients reached peak levels at the second week after admission. NK and NKT cell numbers were negatively correlated with the frequency of HBcAg-specific CTLs (r=-0.266, p=0.05).
  
  
  CONCLUSIONS
  Patients with AHB possess a higher frequency of HBcAg-specific CTLs than CHB patients. The frequency of specific CTLs in AHB patients is correlated with HBeAg clearance indicating that HBV-specific CTLs play an important role in viral clearance and the self-limited process of the disease. Furthermore, NK and NKT cells are likely involved in the early, non-specific immune response to clear the virus.
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China. prof.lijun@gmail.com
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yaping
authors.initials: Y
authors.lastname: Han
authors.forename: Ke
authors.initials: K
authors.lastname: Jin
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Wan
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Zuhu
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D055815:Young Adult
chemical_list: D007371:Interferon-gamma