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Active suppression induced by repetitive self-epitopes protects against EAE development

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Item Type:Article
Title:Active suppression induced by repetitive self-epitopes protects against EAE development
Creators Name:Puentes, F. and Dickhaut, K. and Hofstaetter, M. and Falk, K. and Roetzschke, O.
Abstract:BACKGROUND: Autoimmune diseases result from a breakdown in self-tolerance to autoantigens. Self-tolerance is induced and sustained by central and peripheral mechanisms intended to deviate harmful immune responses and to maintain homeostasis, where regulatory T cells play a crucial role. The use of self-antigens in the study and treatment of a range of autoimmune diseases has been widely described; however, the mechanisms underlying the induced protection by these means are unclear. This study shows that protection of experimental autoimmune disease induced by T cell self-epitopes in a multimerized form (oligomers) is mediated by the induction of active suppression. PRINCIPAL FINDINGS: The experimental autoimmune encephalomyelitis (EAE) animal model for multiple sclerosis was used to study the mechanisms of protection induced by the treatment of oligomerized T cell epitope of myelin proteolipid protein (PLP139-151). Disease protection attained by the administration of oligomers was shown to be antigen specific and effective in both prevention and treatment of ongoing EAE. Oligomer mediated tolerance was actively transferred by cells from treated mice into adoptive hosts. The induction of active suppression was correlated with the recruitment of cells in the periphery associated with increased production of IL-10 and reduction of the pro-inflammatory cytokine TNF-{alpha}. The role of suppressive cytokines was demonstrated by the reversion of oligomer-induced protection after in vivo blocking of either IL-10 or TGF-{beta} cytokines. CONCLUSIONS: This study strongly supports an immunosuppressive role of repeat auto-antigens to control the development of EAE with potential applications in vaccination and antigen specific treatment of autoimmune diseases.
Keywords:Adoptive Transfer, Autoantigens, Cell Proliferation, Cytokines, Experimental Autoimmune Encephalomyelitis, Immunosuppression, Myelin Proteolipid Protein, Peptide Fragments, Protein Multimerization, Quaternary Protein Structure, T-Lymphocyte Epitopes, T-Lymphocytes, Animals, Mice
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:8
Number:5
Page Range:e64888
Date:30 May 2013
Official Publication:https://doi.org/10.1371/journal.pone.0064888
PubMed:View item in PubMed

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