Reduced virus specific T helper cell induction by autologous dendritic cells in patients with chronic hepatitis B – restoration by exogenous interleukin‐12

• Published in: Clinical and experimental immunology Vol. 130; no. 1; pp. 107 - 114
• Main Authors: LÖHR, H. F., PINGEL, S., BÖCHER, W. O., BERNHARD, H., HERZOG‐HAUFF, S., ROSE‐JOHN, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-10-2002; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: antigen presentation; Antigen Presentation - drug effects; Biological and medical sciences; Cell Differentiation - drug effects; Cells, Cultured - immunology; Cells, Cultured - metabolism; chronic hepatitis B; Clinical Studies; Coculture Techniques; Convalescence; dendritic cells; Dendritic Cells - immunology; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Hepatitis B; Hepatitis B Core Antigens - pharmacology; Hepatitis B Surface Antigens - pharmacology; Hepatitis B, Chronic - immunology; Human viral diseases; Humans; Infectious diseases; Interleukin-12 - pharmacology; Interleukin-6 - pharmacology; Lymphokines - metabolism; Medical sciences; Recombinant Fusion Proteins - pharmacology; Stem Cell Factor - pharmacology; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Tetanus Toxoid - pharmacology; Viral diseases; Viral hepatitis; viral persistence interleukin‐12; Human; Dendritic cell; Antigen presentation; Immune response; Cytokine; Hepatic disease; Helper cell; Interleukin 12; Cell subpopulation; Infection; Viral hepatitis B; Chronic; Immunological investigation; Viral disease; T-Lymphocyte; Digestive diseases
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2002.01943.x

SUMMARY
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‐γ 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.