title: Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients.
abstract: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease of the central nervous system. Current therapies decrease the frequency of relapses and limit, to some extent, but do not prevent disease progression. Hence, new therapeutic approaches that modify the natural course of MSneed to be identified. Tolerance induction to self-antigens using monocyte-derived dendritic cells (MDDCs) is a promising therapeutic strategy in autoimmunity. In this work, we sought to generate and characterize tolerogenic MDDCs (tolDCs) from relapsing-remitting (RR) MSpatients, loaded with myelin peptides as specific antigen, with the aim of developing immunotherapeutics for MS. MDDCs were generated from both healthy-blood donors and RR-MSpatients, and MDDCmaturation was induced with a proinflammatory cytokine cocktail in the absence or presence of 1α,25-dihydroxyvitamin-D(3) , a tolerogenicity-inducing agent. tolDCs were generated from monocytes of RR-MSpatients as efficiently as from monocytes of healthy subjects. The RR-MStolDCs expressed a stable semimature phenotype and an antiinflammatory profile as compared with untreated MDDCs. Importantly, myelin peptide-loaded tolDCs induced stable antigen-specific hyporesponsiveness in myelin-reactive T cells from RR-MS patients. These results suggest that myelin peptide-loaded tolDCs may be a powerful tool for inducing myelin-specific tolerance in RR-MS patients.
authors.affiliation: Laboratory of Immunobiology for Research and Diagnosis, Blood and Tissue Bank, Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol, Badalona, Spain.
authors.forename: Dàlia
authors.initials: D
authors.lastname: Raϊch-Regué
authors.forename: Laia
authors.initials: L
authors.lastname: Grau-López
authors.forename: Mar
authors.initials: M
authors.lastname: Naranjo-Gómez
authors.forename: Cristina
authors.initials: C
authors.lastname: Ramo-Tello
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pujol-Borrell
authors.forename: Eva
authors.initials: E
authors.lastname: Martínez-Cáceres
authors.forename: Francesc E
authors.initials: FE
authors.lastname: Borràs
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000628:therapy*; D004676:Myelin Basic Protein / Q000276:immunology* / Q000627:therapeutic use; D010865:Pilot Projects; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein