Split activity of interleukin-10 on antigen capture and antigen presentation by human dendritic cells: definition of a maturative step

Eur J Immunol. 1997 Jan;27(1):26-34. doi: 10.1002/eji.1830270105.

Abstract

Human CD1+ CD14- dendritic cells (DC) can be derived from CD14+ monocytes using granulocyte/monocyte colony-stimulating factor and interleukin (IL)-4. We have previously shown that IL-10 pre-treatment of such DC significantly inhibited their antigen-presenting capacity to CD4+ T cell clones. In this study, we further analyze how IL-10 influences antigen presentation. We first investigated whether IL-10 could alter the early stage of antigen presentation, the capture of antigen. This can be mediated by mannose receptor (MR)-mediated endocytosis and by fluid-phase uptake through macropinocytosis. IL-10-treated DC showed an enhancement of both mechanisms of antigen capture, as indicated by the increase of fluorescein isothiocyanate-dextran uptake through MR and lucifer yellow uptake. However, IL-10-treated DC, irradiated or glutaraldehyde-fixed, were less efficient than untreated DC in stimulating mixed leukocyte reaction as well as in inducing the activation of peptide-specific T cell clones, indicating that IL-10 achieves its effects mainly by modifying the cell surface phenotype of DC. HLA class I and II, as well as intercellular adhesion molecule (ICAM)-1, lymphocyte function-associated antigen-3, B7-1, B7-2 and ICAM-3 expression were either significantly increased or essentially unchanged, and the ability to bind the epitope recognized by the T cell clones was also unaffected regardless of IL-10 treatment. Our study also indicates that as-yet unidentified accessory molecules may play an essential role in T cell activation. Thus, the IL-10-treated DC possess an increased capacity to capture antigen, with a concomitant decreased stimulatory activity. Our study suggests that IL-10-treated DC have the characteristics of highly immature DC (high capture ability, low stimulatory potency) and may represent an early maturative step of human DC of monocytic origin.

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Antigens / metabolism*
  • Antigens, CD / metabolism
  • Antigens, Differentiation*
  • Antigens, Surface / metabolism
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • CD58 Antigens / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cell Compartmentation
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Down-Regulation
  • Endocytosis
  • HLA Antigens / metabolism
  • Humans
  • Immunophenotyping
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-10 / immunology*
  • Iodide Peroxidase / immunology
  • Lectins, C-Type*
  • Mannose Receptor
  • Mannose-Binding Lectins*
  • Membrane Glycoproteins / metabolism
  • Receptors, Cell Surface / metabolism
  • T-Lymphocytes / immunology
  • Time Factors
  • Up-Regulation

Substances

  • Antigens
  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Surface
  • B7-1 Antigen
  • B7-2 Antigen
  • CD58 Antigens
  • CD86 protein, human
  • Cell Adhesion Molecules
  • HLA Antigens
  • ICAM3 protein, human
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Membrane Glycoproteins
  • Receptors, Cell Surface
  • Intercellular Adhesion Molecule-1
  • Interleukin-10
  • Iodide Peroxidase