Fulfilling the dream: tolerogenic dendritic cells to treat multiple sclerosis

Authors

  • Catharina C. Gross,

    1. Department of Inflammatory Disorders of the Nervous System and Neurooncology, Neurology Clinic, University of Münster, Münster, Germany
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  • Helmut Jonuleit,

    1. Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
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  • Heinz Wiendl

    Corresponding author
    1. Department of Inflammatory Disorders of the Nervous System and Neurooncology, Neurology Clinic, University of Münster, Münster, Germany
    • Department of Inflammatory Disorders of the Nervous System and Neurooncology, Neurology Clinic, University of Münster, Albert-Schweizer-Campus 1, Building Fax: +49-(0)251-8346812 A10, 48149 Münster, Germany
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Abstract

Autoimmune diseases including multiple sclerosis (MS) are the result of an imbalanced immune tolerance network. Dendritic cells (DCs) are key players in both initiating immunity (immunogenic DCs) and regulating immune responses (tolerogenic DCs = tolDCs) and are potential targets for the treatment of MS. While the immunogenic potential of DCs in fighting infection and cancer has been well established, approaches that exploit their tolerogenic features to promote transplantation tolerance and autoimmunity have emerged only more recently. TolDCs usually maintain antigen-specific T-cell tolerance either directly by inducing anergy, apoptosis, or phenotype skewing or indirectly by induction of regulatory T (Treg) cells. The use of ex vivo-generated tolDCs is an experimental approach to achieve tolerance towards myelin-antigen-specific CD4+ T cells. In the article by Raϊch-Regué and colleagues (Eur. J. Immunol. 2011. 42:772-783) in this issue of the European Journal of Immunology, advances in human tolDC preparation and promise for autologous therapy are described. These findings raise hopes of achieving the "ideal" of a highly-specific, causally-oriented immune intervention for central nervous system (CNS) autoimmunity in MS. However, recent experience with antigen-specific immune interventions in MS and some general caveats associated with cell-based-therapies highlight the challenges for clinical translation of the "immunologist's dream" of treating autoimmunity as discussed in this Commentary.

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