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Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant tolerance

Item Type:Article
Title:Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant tolerance
Creators Name:Piaggio, E. and Mars, L.T. and Cassan, C. and Cabarrocas, J. and Hofstaetter, M. and Desbois, S. and Bergereau, E. and Roetzschke, O. and Falk, K. and Liblau, R.S.
Abstract:Immunotherapy by using multimerized self-peptides has demonstrated a clear protective effect on experimental models of autoimmune diseases. However, the mechanisms involved remain ill-defined. Here we have evaluated the therapeutic efficacy of multimerized self-peptides at the effector phase of autoimmune diabetes and examined their mechanisms of action. Diabetes was induced in rat insulin promoter-hemagglutinin (HA) mice expressing HA in pancreatic beta-cells by adoptive transfer of HA110-119-specific T helper 1 cells. Complete protection was provided by low doses of the HA 4-mer consisting of four covalently linked linear HA107-119 peptides. In vivo, the 4-mer appeared to act directly on the pathogenic HA-specific T helper 1 cells and indirectly by activation/recruitment of lymphocytes with regulatory properties so that mice became resistant to a second transfer of diabetogenic T cells. This effect was associated with a recruitment of Foxp3(+) CD4 T cells around islets. Moreover, we show that dominant protection from autoimmunity was transferable by spleen cells, and that development of this regulatory population was crucially dependent on the lymphocytes from treated rat insulin promoter-HA mice. Thus, immunotherapy using multimerized epitopes emerges as a promising strategy in view of the current identification of self-epitopes that are major targets of the pathogenic CD4 T cell response in autoimmune diseases.
Keywords:Autoimmunity immune tolerance, Immunotherapy, Regulatory T cells, Foxp3, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:9393-9398
Date:29 May 2007
Official Publication:https://doi.org/10.1073/pnas.0610423104
PubMed:View item in PubMed

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