title: Dendritic cells pulsed with antigen-specific apoptotic bodies prevent experimental type 1 diabetes.
abstract: Dendritic cells (DCs) are powerful antigen-presenting cells capable of maintaining peripheral tolerance. The possibility to generate tolerogenic DCs opens new therapeutic approaches in the prevention or remission of autoimmunity. There is currently no treatment inducing long-term tolerance and remission in type 1 diabetes (T1D), a disease caused by autoimmunity towards beta cells. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow islet regeneration. Apoptotic cells--a source of autoantigens--are cleared rapidly by macrophages and DCs through an immunologically silent process that contributes to maintaining tolerance. Our aims were to prevent T1D and to evaluate the re-establishment of peripheral tolerance using autologous DCs pulsed in vitro with apoptotic bodies from beta cells. Immature DCs derived from bone marrow of non-obese diabetic (NOD) mice were obtained and pulsed with antigen-specific apoptotic bodies from the beta cell line NIT-1. Those DCs that phagocytosed apoptotic cells diminished the expression of co-stimulatory molecules CD40 and CD86 and reduced secretion of proinflammatory cytokines. Moreover, these cells were resistant to increase the expression of co-stimulatory molecules after lipopolysaccharide activation. The administration of these cells to NOD transgenic mice expressing interferon-beta in their insulin-producing cells, a model of accelerated autoimmune diabetes, decreased diabetes incidence significantly and correlated positively with insulitis reduction. DCs pulsed with apoptotic cells that express disease-associated antigens constitutes a promising strategy to prevent T1D.
authors.affiliation: Laboratory of Immunobiology for Research and Diagnosis-Blood and Tissue Bank (LIRAD-BST), Germans Trias i Pujol Research Institute, Department of Cellular Biology, Physiology and Immunology, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Marin-Gallen
authors.forename: X
authors.initials: X
authors.lastname: Clemente-Casares
authors.forename: R
authors.initials: R
authors.lastname: Planas
authors.forename: I
authors.initials: I
authors.lastname: Pujol-Autonell
authors.forename: J
authors.initials: J
authors.lastname: Carrascal
authors.forename: J
authors.initials: J
authors.lastname: Carrillo
authors.forename: R
authors.initials: R
authors.lastname: Ampudia
authors.forename: J
authors.initials: J
authors.lastname: Verdaguer
authors.forename: R
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: F E
authors.initials: FE
authors.lastname: Borràs
authors.forename: M
authors.initials: M
authors.lastname: Vives-Pi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D004705:Endocytosis; D000939:Epitopes; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000473:pathology; D016899:Interferon-beta / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013047:Specific Pathogen-Free Organisms
chemical_list: D001324:Autoantigens; D000939:Epitopes; D008070:Lipopolysaccharides; D011993:Recombinant Fusion Proteins; D016899:Interferon-beta