title: Hepatitis B virus (HBV)-specific T-cell responses to recombinant HBV core protein in patients with normal liver function and co-infected with chronic HBV and human immunodeficiency virus 1 (HIV-1).
abstract: BACKGROUND
  Little is known about HBV-specific T-cell responses in chronic Hepatitis B patients (HBV) that are co-infected with Human immunodeficiency virus type 1 (HIV-1), especially those with normal alanine aminotransferase (ALT) levels.
  
  
  METHODS
  Twenty-five patients with chronic HBV (11 hepatitis B e antigen [HBeAg]-positive, 14 HBeAg-negative) were enrolled in a cross-sectional study. A longitudinal study as also conducted in which follow-up was done at 3, 12, and 24 months, after acute HIV-1 infection, in 11 individuals who also had chronic HBV. Peripheral blood mononuclear cells were stimulated with recombinant HBV surface protein (S protein), core protein (C protein) or gag peptide. IFN-γ-secreting T cells were identified by ELISPOT assay.
  
  
  RESULTS
  In the cross-sectional study, co-infected chronic HBV patients had lower C protein-specific T-cell responses compared with mono-infected individuals, though the difference was not significant. In co-infected, chronic HBV patients, the magnitude of C protein-specific T-cell responses was significantly greater in HBeAg-positive subjects compared to HBeAg-negative subjects (p = 0.011). C protein-specific T-cell responses were positively correlated with HBV viral load (rs = 0.40, p = 0.046). However, gag-specific T-cell responses were negatively correlated with HIV viral load (rs = -0.44, p = 0.026) and positively correlated with CD4+ count (rs = 0.46, p = 0.021). The results were different in mono-infected individuals. PBMCs from co-infected HBeAg-positive patients secreted more specific-IFN-γ in cultured supernatants compared with PBMCs from co-infected HBeAg-negative patients (p = 0.019). In the longitudinal study, S protein- and C protein-specific T-cell responses were decreased as the length of follow-up increased (p = 0.034, for S protein; p = 0.105, for C protein). Additionally, the S protein- and C protein-specific T-cell responses were significantly higher in HBeAg-positive patients than in HBeAg-negative patients at 3 and 12 months after HIV-1 infection (all p < 0.05), but not at 24 months. A positive correlation (trend) was found between C protein-specific T-cell responses and HBV viral load at 3 and 12 months after HIV-1 infection.
  
  
  CONCLUSIONS
  HBV-specific T-cell responses to recombinant HBV core protein were reduced in chronic HBV patients co-infected with HIV-1. The reduced C protein-specific T cell responses were positively correlated with HBV viral load in co-infected, chronic HBV patients.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Hanqian
authors.initials: H
authors.lastname: Xing
authors.forename: Xia
authors.initials: X
authors.lastname: Feng
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Huiping
authors.initials: H
authors.lastname: Yan
mesh_terms: D000328:Adult; D000368:Aged; D060085:Coinfection / Q000276:immunology*; D003430:Cross-Sectional Studies; D004279:DNA, Viral / Q000097:blood; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma