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dc.contributor.authorGibson, V. B.-
dc.contributor.authorNikolic, T.-
dc.contributor.authorPearce, V. Q.-
dc.contributor.authorDemengeot, J.-
dc.contributor.authorRoep, B. O.-
dc.contributor.authorPeakman, M.-
dc.identifier.citationGibson, V. B., Nikolic, T., Pearce, V. Q., Demengeot, J., Roep, B. O. and Peakman, M. (2015), Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model. Clin Exp Immunol, 182: 251–260. doi:10.1111/cei.12687pt_PT
dc.descriptionTThis deposit is composed by a publication in which the IGC's authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and can only be accessed by two ways: either by requesting a legal copy from the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636887/pt_PT
dc.descriptionThis publication hasn't any creative commons license associated.pt_PT
dc.description.abstractPeptide immunotherapy (PIT) is a targeted therapeutic approach, involving administration of disease-associated peptides, with the aim of restoring antigen-specific immunological tolerance without generalized immunosuppression. In type 1 diabetes, proinsulin is a primary antigen targeted by the autoimmune response, and is therefore a strong candidate for exploitation via PIT in this setting. To elucidate the optimal conditions for proinsulin-based PIT and explore mechanisms of action, we developed a preclinical model of proinsulin autoimmunity in a humanized HLA-DRB1*0401 transgenic HLA-DR4 Tg mouse. Once proinsulin-specific tolerance is broken, HLA-DR4 Tg mice develop autoinflammatory responses, including proinsulin-specific T cell proliferation, interferon (IFN)-γ and autoantibody production. These are preventable and quenchable by pre- and post-induction treatment, respectively, using intradermal proinsulin-PIT injections. Intradermal proinsulin-PIT enhances proliferation of regulatory [forkhead box protein 3 (FoxP3(+))CD25(high) ] CD4 T cells, including those capable of proinsulin-specific regulation, suggesting this as its main mode of action. In contrast, peptide delivered intradermally on the surface of vitamin D3-modulated (tolerogenic) dendritic cells, controls autoimmunity in association with proinsulin-specific IL-10 production, but no change in regulatory CD4 T cells. These studies define a humanized, translational model for in vivo optimization of PIT to control autoimmunity in type 1 diabetes and indicate that dominant mechanisms of action differ according to mode of peptide delivery.pt_PT
dc.description.sponsorshipEuropean Union's (EU FP7) Large-Scale Focused Collaborative Research Project on Natural Immunomodulators as Novel Immunotherapies for Type 1 Diabetes grant: (NAIMIT, 241447); UK Department of Health via the National Institute for Health Research (NIHR); Biomedical Research Centre Award to Guy's and St Thomas’ National Health Service Foundation Trust; King's College London; Dutch Diabetes Research Foundation; European Commission Seventh Framework Programme grants: (PEVNET and EE-ASI).pt_PT
dc.subjectregulatory T cellspt_PT
dc.subjectT cellspt_PT
dc.titleProinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized modelpt_PT
degois.publication.titleClinical and Experimental Immunologypt_PT
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