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Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model

2015-12Journal article Restricted access
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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.date.accessioned2018-03-05T16:04:51Z
dc.date.available2018-03-05T16:04:51Z
dc.date.issued2015-12
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.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
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.identifier.doi10.1111/cei.12687pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/847
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationNovel immunotherapies for type 1 diabetes.
dc.relationPersistent virus infection as a cause of pathogenic inflammation in type 1 diabetes - an innovative research program of biobanks and expertise
dc.relationBeta cell preservation via antigen-specific immunotherapy in Type 1 Diabetes: Enhanced Epidermal Antigen Delivery Systems.
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1111/cei.12687/abstractpt_PT
dc.subjectantigens/peptides/epitopespt_PT
dc.subjectAutoimmunitypt_PT
dc.subjectdiabetespt_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
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleNovel immunotherapies for type 1 diabetes.
oaire.awardTitlePersistent virus infection as a cause of pathogenic inflammation in type 1 diabetes - an innovative research program of biobanks and expertise
oaire.awardTitleBeta cell preservation via antigen-specific immunotherapy in Type 1 Diabetes: Enhanced Epidermal Antigen Delivery Systems.
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/241447/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/261441/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/305305/EU
oaire.citation.endPage260pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage251pt_PT
oaire.citation.titleClinical and Experimental Immunologypt_PT
oaire.citation.volume182pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamFP7
oaire.fundingStreamFP7
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationaa295658-7788-4d22-80ef-b389ea280ea8
relation.isProjectOfPublication46e7346a-4f5d-41e3-9564-7096b8271d5d
relation.isProjectOfPublicationb8c49efa-ed52-4fbb-b20e-2e64d3473560
relation.isProjectOfPublication.latestForDiscoveryaa295658-7788-4d22-80ef-b389ea280ea8

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