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Prospects for Antigen-Specific Tolerance Based Therapies for the Treatment of Multiple Sclerosis

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Molecular Basis of Multiple Sclerosis

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 51))

Abstract

A primary focus in autoimmunity is the breakdown of central and peripheral tolerance resulting in the survival and eventual activation of autoreactive T cells. As CD4+ T cells are key contributors to the underlying pathogenic mechanisms responsible for onset and progression of most autoimmune diseases, they are a logical target for therapeutic strategies. One method for restoring self-tolerance is to exploit the endogenous regulatory mechanisms that govern CD4+ T cell activation. In this review, we discuss tolerance strategies with the common goal of inducing antigen (Ag)-specific tolerance. Emphasis is given to the use of peptide-specific tolerance strategies, focusing on ethylene carbodiimide (ECDI)-peptide-coupled cells (Ag-SP) and nonmitogenic anti-CD3, which specifically target the T cell receptor (TCR) in the absence of costimulatory signals. These approaches induce a TCR signal of insufficient strength to cause CD4+ T cell activation and instead lead to functional T cell anergy/deletion and activation of Ag-specific induced regulatory T cells (iTregs) while avoiding generalized long-term immunosuppression.

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  1. Department of Microbiology-Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Tarry 6-718, 303 E. Chicago Ave, Chicago, IL, 60611, USA

    Danielle M. Turley & Stephen D. Miller

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  1. Danielle M. Turley
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  2. Stephen D. Miller
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Correspondence to Stephen D. Miller .

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  1. Institut für Neuroimmunologie und, Klinische Multiple-Sklerose-Forschung, Universitätsklinikum Hamburg-Eppendorf, Falkenried 94, Hamburg, 20251, Germany

    Roland Martin

  2. , Clinical Department of Neurology, Innsbruck Medical University, Anichstrasse 35, Innsbruck, 6020, Austria

    Andreas Lutterotti

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© 2009 Springer Berlin Heidelberg

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Turley, D.M., Miller, S.D. (2009). Prospects for Antigen-Specific Tolerance Based Therapies for the Treatment of Multiple Sclerosis. In: Martin, R., Lutterotti, A. (eds) Molecular Basis of Multiple Sclerosis. Results and Problems in Cell Differentiation, vol 51. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2008_13

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