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

Clin Exp Immunol. 2002 Oct;130(1):107-14. doi: 10.1046/j.1365-2249.2002.01943.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / drug effects*
  • Cell Differentiation / drug effects
  • Cells, Cultured / immunology
  • Cells, Cultured / metabolism
  • Coculture Techniques
  • Convalescence
  • Dendritic Cells / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Hepatitis B Core Antigens / pharmacology
  • Hepatitis B Surface Antigens / pharmacology
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Interleukin-12 / pharmacology*
  • Interleukin-6 / pharmacology
  • Lymphokines / metabolism
  • Recombinant Fusion Proteins / pharmacology
  • Stem Cell Factor / pharmacology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Tetanus Toxoid / pharmacology

Substances

  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Interleukin-6
  • Lymphokines
  • Recombinant Fusion Proteins
  • Stem Cell Factor
  • Tetanus Toxoid
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor