Immune tolerance in multiple sclerosis
- 13 April 2011
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 241 (1), 228-240
- https://doi.org/10.1111/j.1600-065x.2011.01016.x
Abstract
Summary: Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously activated by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T‐cell tolerance to myelin antigens and to understand how some myelin‐specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin‐specific T cells, as most myelin‐specific T cells are eliminated by clonal deletion in the thymus. Self‐reactive T cells that escape central tolerance are generally capable only of low‐avidity interactions with antigen‐presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin‐specific T cells have been identified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4+ myelin‐specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8+ myelin‐specific T cells.Keywords
This publication has 83 references indexed in Scilit:
- Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRsNature Immunology, 2010
- AIRE in the thymus and beyondCurrent Opinion in Immunology, 2009
- Pathogenic MOG-reactive CD8+ T cells require MOG-reactive CD4+ T cells for sustained CNS inflammation during chronic EAEJournal of Neuroimmunology, 2009
- Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cellsThe Journal of Experimental Medicine, 2009
- Autoimmune T cell responses in the central nervous systemNature Reviews Immunology, 2009
- Crosspresentation by nonhematopoietic and direct presentation by hematopoietic cells induce central tolerance to myelin basic proteinProceedings of the National Academy of Sciences of the United States of America, 2008
- Presentation of a determinant by MHC class II can be prevented through competitive capture by a flanking determinant on a multideterminant peptideJournal of Autoimmunity, 2008
- HLA-A Confers an HLA-DRB1 Independent Influence on the Risk of Multiple SclerosisPLOS ONE, 2007
- Myelin oligodendrocyte glycoprotein–specific T and B cells cooperate to induce a Devic-like disease in miceJCI Insight, 2006
- Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell/B cell cooperationJCI Insight, 2006