Restoration in vitro of impaired T-cell responses in patients with chronic hepatitis B by autologous dendritic cells loaded with hepatitis B virus proteins (R2).
BACKGROUND
The purpose of the present paper was to investigate dendritic cell (DC) and T-cell functions in patients with chronic hepatitis B (CHB) and determine whether therapeutic DC vaccines could restore T-cell function in those patients in vitro.


METHODS
Twelve patients with CHB and 10 normal control subjects with positivity for antibodies to hepatitis B surface and core antigens (anti-HBs and anti-HBc positivity) were enrolled in the present study. Phenotype analysis and allogeneic mixed lymphocyte reaction assay of DC from CHB patients and normal controls were made in the absence or presence of a cocktail of cytokines: interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), IL-6 and tumor necrosis factor-alpha (TNF-alpha). Autologous T-cell proliferation assays and the enzyme-linked immunospot (ELISPOT) method for detecting interferon-gamma (IFN-gamma)-producing CD8(+) T cells were used to evaluate the efficacy of DC loaded in vitro with HBsAg or HBcAg.


RESULTS
The DC from CHB patients had a lower expression of costimulatory molecules CD80, CD86 and impaired allogeneic mixed lymphocyte reaction capacity compared to those from normal controls. However, the impaired DC function could be restored partially by cytokine cocktail supplemented in vitro. Mature DC loaded with HBsAg or HBcAg showed a greater capacity for autologous T-cell proliferation and antigen-specific IFN-gamma production than immature DC. Moreover, as a DC -loading antigen, HBcAg was more immunogenic than HBsAg.


CONCLUSIONS
The impaired function of DC in patients with CHB may be restored by supplementation in vitro with a cocktail of cytokines, and therapeutic DC vaccines might be effective to treat CHB infection in humans.
Duan
Xue-Zhang
XZ
Department of Microbiology, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100083, China. dxzh@cgw.net.cn
He
Hong-Xia
HX
Zhuang
Hui
H
D000328:Adult; D001681:Biological Assay; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D016207:Cytokines; D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D014764:Viral Proteins; D007371:Interferon-gamma