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Title: Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers.
Author: Izquierdo, Cristina
Ortiz, Angela
Presa, Maximiliano
Malo, Sara
Montoya, Anna
Garabatos Leitón, Ma. Nahir
Mora, Conchi
Verdaguer, Joan
Stratmann, Thomas
Keywords: Immunologia
Malalties autoimmunitàries
Anticossos monoclonals
Autoimmune diseases
Monoclonal antibodies
Issue Date: 25-May-2018
Publisher: Nature Publishing Group
Abstract: Type 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.
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It is part of: Scientific Reports, 2018, vol. 8, num. 8106
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ISSN: 2045-2322
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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