title: Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection.
abstract: A defect in specific T cell immunity has long been assumed to be the central mechanism of persistent Hepatitis B virus (HBV) infection. Recent studies on HBV transgenic mice have suggested, however, that functional deficit of dendritic cells (DC) was an underlying cause for the T cell dysfunction. The functions of monocyte-derived DC were determined by studying 75 subjects that included chronic hepatitis B patients with low or high HBV load; antibody to hepatitis B surface antigen (anti-HBs) positive individuals who had recovered completely from previous acute HBV infection; healthy donors who had received hepatitis B vaccination and were anti-HBs positive; and immunologically naïve to HBV or the vaccine individual. Impaired interactions between monocyte-derived DC and T cells were shown in chronic HBV infection patients, especially in those with active virus replication. The dysfunctions included: (i) failure of DC to increase human leukocyte antigen (HLA-II), B7 expression and interleukin-12 secretion in responses to hepatitis B surface antigen (HBsAg), (ii) defective induction of T cell proliferative response to HBsAg, (iii) failure to activate T cells to produce cytokines and (iv) deficit in the induction of antigen specific cytotoxic T lymphocytes (CTLs). In vitro treatment of DC with tumour necrosis factor-alpha improved HLA-II and B7 expression, as well as Th cell and CTL responses. It is concluded that defective DC-T cell interactions may account for the specific T cell immune defects in chronic HBV infection. Immunotherapy that aims at restoring DC functions could offer a new opportunity for effectively managing persistent HBV infections.
authors.affiliation: Department of Microbiology, The University of Hong Kong, Hong Kong.
authors.forename: B J
authors.initials: BJ
authors.lastname: Zheng
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: D
authors.initials: D
authors.lastname: Qu
authors.forename: K L
authors.initials: KL
authors.lastname: Siu
authors.forename: T W
authors.initials: TW
authors.lastname: Lam
authors.forename: H Y
authors.initials: HY
authors.lastname: Lo
authors.forename: S S
authors.initials: SS
authors.lastname: Lee
authors.forename: Y M
authors.initials: YM
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D016022:Case-Control Studies; D002450:Cell Communication; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005802:Genes, MHC Class II; D006510:Hepatitis B Antibodies / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D017325:Hepatitis B Vaccines