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

Authors

  • Dàlia Raϊch-Regué,

    1. Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank (BST). Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
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  • Laia Grau-López,

    1. Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank (BST). Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
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  • Mar Naranjo-Gómez,

    1. Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank (BST). Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
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  • Cristina Ramo-Tello,

    1. Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank (BST). Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
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  • Ricardo Pujol-Borrell,

    1. Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank (BST). Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
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  • Eva Martínez-Cáceres,

    Corresponding author
    1. Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank (BST). Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
    • LIRAD-BST. Institut d'Investigació Germans Trias i Pujol, Ctra. del Canyet s/n, Edifici "Escoles," 08916 Badalona (Barcelona) Spain, Fax: +34-93-4978668
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  • Francesc E. Borràs

    Corresponding author
    1. Laboratory of Immunobiology for Research and Diagnosis (LIRAD), Blood and Tissue Bank (BST). Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Institut d'Investigació Germans Trias i Pujol (IGTP), Badalona, Spain
    • LIRAD-BST. Institut d'Investigació Germans Trias i Pujol, Ctra. del Canyet s/n, Edifici "Escoles," 08916 Badalona (Barcelona) Spain, Fax: +34-93-4978668
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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-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.

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