Prospects for antigen-specific tolerance based therapies for the treatment of multiple sclerosis

Danielle M. Turley, Stephen D. Miller

Research output: Chapter in Book/Report/Conference proceedingChapter

25 Scopus citations

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.

Original languageEnglish (US)
Title of host publicationMolecular Basis of Multiple Sclerosis
Subtitle of host publicationThe Immune System
EditorsRoland Martin, Andreas Lutterotti
Pages217-235
Number of pages19
DOIs
StatePublished - 2010

Publication series

NameResults and Problems in Cell Differentiation
Volume51
ISSN (Print)0080-1844
ISSN (Electronic)1861-0412

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Turley, D. M., & Miller, S. D. (2010). Prospects for antigen-specific tolerance based therapies for the treatment of multiple sclerosis. In R. Martin, & A. Lutterotti (Eds.), Molecular Basis of Multiple Sclerosis: The Immune System (pp. 217-235). (Results and Problems in Cell Differentiation; Vol. 51). https://doi.org/10.1007/400_2008_13