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dc.contributor.authorIzquierdo, Cristina
dc.contributor.authorZarama Ortiz, Angela
dc.contributor.authorPresa, Maximiliano
dc.contributor.authorMalo, Sara
dc.contributor.authorMontoya, Anna
dc.contributor.authorGarabatos, Nahir
dc.contributor.authorMora Giral, Concepció
dc.contributor.authorVerdaguer Autonell, Joan
dc.contributor.authorStratmann, Thomas
dc.description.abstractType 1 diabetes can be overcome by regulatory T cells (Treg) in NOD mice yet an efficient method to generate and maintain antigen-specific Treg is difficult to come by. Here, we devised a combination therapy of peptide/MHC tetramers and IL-2/anti-IL-2 monoclonal antibody complexes to generate antigen-specific Treg and maintain them over extended time periods. We first optimized treatment protocols conceived to obtain an improved islet-specific Treg/effector T cell ratio that led to the in vivo expansion and activation of these Treg as well as to an improved suppressor function. Optimized protocols were applied to treatment for testing diabetes prevention in NOD mice as well as in an accelerated T cell transfer model of T1D. The combined treatment led to robust protection against diabetes, and in the NOD model, to a close to complete prevention of insulitis. Treatment was accompanied with increased secretion of IL-10, detectable in total splenocytes and in Foxp3− CD4 T cells. Our data suggest that a dual protection mechanism takes place by the collaboration of Foxp3+ and Foxp3− regulatory cells. We conclude that antigen-specific Treg are an important target to improve current clinical interventions against this disease.ca_ES
dc.description.sponsorshipThis work was supported by grants from the Spanish Ministry of Economy, Industry, the Juvenile Diabetes Research Foundation, and Competition and European Regional Development Funds (FEDER; SAF2010-18548 and SAF2011-29319 to T.S.; SAF2016-77227-R and SAF2013-45140-R to J.V. and T.S., SAF2008-02536 and SAF2014-55077-R to C.M.). Research of J.V. was also supported by CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) that is an initiative from the Instituto de Salud Carlos III (Spain). C.I. received a FPU fellowship. C.M., J.V. and T.S. are Serra Húnter Fellows.ca_ES
dc.publisherNature Publishing Groupca_ES
dc.relation.isformatofReproducció del document publicat a
dc.relation.ispartofScientific Reports, 2018, vol. 8, núm. 8106, p.1-14ca_ES
dc.rightscc-by (c) Izquierdo et al., 2018ca_ES
dc.titleTreatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramersca_ES

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cc-by (c) Izquierdo et al., 2018
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