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Thioreductase containing epitopes inhibit the development of type 1 diabetes in the NOD mouse model

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Malek Abrahimians, Elin [UCL] Vander Elst, Luc P. Carlier, Vincent A. Saint-Remy, Jean-Marie

Autoreactive CD4+ T cells recognizing islet-derived antigens play a primary role in type 1 diabetes. Specific suppression of such cells therefore represents a strategic target for the cure of the disease. We have developed a methodology by which CD4+ T cells acquire apoptosis-inducing properties on antigen-presenting cells after cognate recognition of natural sequence epitopes. We describe here that inclusion of a thiol-disulfide oxidoreductase (thioreductase) motif within the flanking residues of a single MHC class II-restricted GAD65 epitope induces GAD65-specific cytolytic CD4+ T cells (cCD4+ T). The latter, obtained either in vitro or by active immunization, acquire an effector memory phenotype and lyse APCs by a Fas-FasL interaction. Further, cCD4+ T cells eliminate by apoptosis activated bystander CD4+ T cells recognizing alternative epitopes processed by the same APC. Active immunization with a GAD65 class II-restricted thioreductase-containing T cell epitope protects mice from diabetes and abrogates insulitis. Passive transfer of in vitro-elicited cCD4+ T cells establishes that such cells are efficient in suppressing autoimmunity. These findings provide strong evidence for a new vaccination strategy to prevent type 1 diabetes.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2016
Language Anglais
Journal information "Frontiers in Immunology" - Vol. 7, p. 67 [1-10] (2016)
Peer reviewed yes
Publisher Frontiers Media ((Switzerland) Lausanne)
e-issn 1664-3224
Publication status Publié
Affiliations UCL - SSS/IREC/PEDI - Pôle de Pédiatrie
UCL - (SLuc) Service de pédiatrie spécialisée
Links
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Bibliographic reference Malek Abrahimians, Elin ; Vander Elst, Luc P. ; Carlier, Vincent A. ; Saint-Remy, Jean-Marie. Thioreductase containing epitopes inhibit the development of type 1 diabetes in the NOD mouse model. In: Frontiers in Immunology, Vol. 7, p. 67 [1-10] (2016)
Permanent URL http://hdl.handle.net/2078.1/172239