Stable antigen‐specific T‐cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients

• Published in: European journal of immunology Vol. 42; no. 3; pp. 771 - 782
• Main Authors: Raϊch‐Regué, Dàlia, Grau‐López, Laia, Naranjo‐Gómez, Mar, Ramo‐Tello, Cristina, Pujol‐Borrell, Ricardo, Martínez‐Cáceres, Eva, Borràs, Francesc E.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.03.2012; Wiley Subscription Services, Inc
• Subjects: 1α,25‐dihydroxyvitamin D3; Adult; Autoimmune disease; Autoimmune diseases; Case-Control Studies; Cell Differentiation - immunology; Cell immunotherapy; Cytokines - immunology; DCs; Dendritic Cells - cytology; Dendritic Cells - immunology; Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte - immunology; Female; Flow Cytometry; Humans; Immune Tolerance - immunology; Immunotherapy, Adoptive - methods; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - therapy; Myelin Basic Protein - immunology; Myelin Basic Protein - therapeutic use; Pilot Projects; Statistics, Nonparametric; T-Lymphocytes - immunology; Tolerance induction
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.201141835

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‐D3, 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.