Reduced virus specific T helper cell induction by autologous dendritic cells in patients with chronic hepatitis B - restoration by exogenous interleukin-12.
Insufficient stimulatory capacities of autologous dendritic cells (DC) may contribute in part to impaired T cell stimulation and therefore viral persistence in patients with chronic hepatitis B virus (HBV) infection. In order to characterize the antigen presenting functions of DC from chronic HBV carriers and controls antigen specific T cell responses were analysed. CD34+ peripheral blood progenitor cells were differentiated to immature DC in the presence of GM-CSF, IL-6/IL-6R fusion protein and stem cell factor. Proliferative CD4+ T cell responses and specific cytokine release were analysed in co-cultures of DC pulsed with HBV surface and core antigens or tetanus toxoid and autologous CD4+ T cells. Cultured under identical conditions DC from chronic HBV carriers, individuals with acute resolved hepatitis B and healthy controls expressed similar phenotypical markers but chronic HBV carriers showed less frequent and weaker HBV antigen specific proliferative T helper cell responses and secreted less interferon-gamma while responses to the tetanus toxoid control antigen was not affected. Preincubation with recombinant IL-12 enhanced the HBV specific immune reactivities in chronic HBV patients and controls. In conclusion, the weak antiviral immune responses observed in chronic hepatitis B may result in part from insufficient T cell stimulating capacities of DC. Immunostimulation by IL-12 restored the HBV antigen specific T cell responses and could have some therapeutical benefit to overcome viral persistence.
Löhr
H F
HF
Department of Internal Medicine, Johannes-Gutenberg-University Mainz, Mainz, Germany. loehr@mail.uni-maiz.de
Pingel
S
S
Böcher
W O
WO
Bernhard
H
H
Herzog-Hauff
S
S
Rose-John
S
S
Galle
P R
PR
D017951:Antigen Presentation / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003289:Convalescence; D003713:Dendritic Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006512:Hepatitis B Core Antigens / Q000494:pharmacology; D006514:Hepatitis B Surface Antigens / Q000494:pharmacology; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008222:Lymphokines / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D013745:Tetanus Toxoid / Q000494:pharmacology
D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D015850:Interleukin-6; D008222:Lymphokines; D011993:Recombinant Fusion Proteins; D019089:Stem Cell Factor; D013745:Tetanus Toxoid; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor