title: Split activity of interleukin-10 on antigen capture and antigen presentation by human dendritic cells: definition of a maturative step.
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.
authors.affiliation: The Mathilda & Terence Kennedy Institute of Rheumatology, Sunley Division, London, GB.
authors.forename: A S
authors.initials: AS
authors.lastname: Morel
authors.forename: S
authors.initials: S
authors.lastname: Quaratino
authors.forename: D C
authors.initials: DC
authors.lastname: Douek
authors.forename: M
authors.initials: M
authors.lastname: Londei
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D000941:Antigens / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation; D000954:Antigens, Surface / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D018968:CD58 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002451:Cell Compartmentation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D004705:Endocytosis; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology*; D007453:Iodide Peroxidase / Q000276:immunology; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018968:CD58 Antigens; C497964:CD86 protein, human; D015815:Cell Adhesion Molecules; D006680:HLA Antigens; C483616:ICAM3 protein, human; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D007453:Iodide Peroxidase