Obiettivo Type 1 diabetes (T1D) is thought to be T-cell mediated auto-immune disease, where auto-aggressive CD4+ and CD8+ lymphocytes target and destroy the insulin producing pancreatic b-cells. During the last decade several studies focused on different immune-based therapies to treat or prevent T1D.Numerous data point towards two promising immune interventions:(1) The antigen specific prevention of T1D for example with DNA vaccines, proinsulin, GAD and insulin B chain, which can prevent T1D in more than 50% RIP-L CMV transgenic or NOD mice. Unfortunately, the protective effect of such strategies was only observed when the antigen was given early during the prediabetic phase.(2) In contrast, non-mitogenic anti-CD3 antibody is able to revert recent-onset TID in NOD m ice, which was initially discovered by Lucienne Chatenoud. This antibody has already been tested by Jeff Bluestone and Kevan Herold clinically and preserved C-peptide levels over the first year in recent-onset diabetics.The aim of our present study is based on the idea that combination of anti-CD3 systemic therapy with antigen specific approaches might result in a synergistic effect. We believe that anti-CD3 will act to "reset" the immune system, then leaving a window for therapeutic intervention with anti gen specific treatments to induce regulation that can maintain long-term tolerance in T1D.This approach will be tested pre-clinically by using the NOD and RIP-LCMV transgenic mouse models treated with a commercial anti-CD3 Fab'2 in combination with islet specific-antigens (administered as DNA, peptides or full protein) after recent onset of T1D. In our opinion, this strategy will increase efficacy of antigen specific immunizations by opening a window for re-direction of the existing autoreactive response and/or de novo induction of autoantigen specific (adaptive) regulatory T cells. We believe the risk for adverse allergic reactions as well as aggravation of the autoimmune process will be lowered through. Campo scientifico medical and health sciencesbasic medicineimmunologyimmunisationnatural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines Parole chiave Autoimmunity anti-CD3 antigen-specific immuno-intervention regulatory T cells type 1 diabetes Programma(i) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Argomento(i) MOBILITY-2.2 - Marie Curie Outgoing International Fellowships (OIF) Invito a presentare proposte FP6-2002-MOBILITY-6 Vedi altri progetti per questo bando Meccanismo di finanziamento OIF - Marie Curie actions-Outgoing International Fellowships Coordinatore CENTRE NATIONAL POUR LA RECHERCHE SCIENTIFIQUE Contributo UE Nessun dato Indirizzo Route de Mende n°1919 MONTPELLIER Francia Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato Partecipanti (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY Stati Uniti Contributo UE Nessun dato Indirizzo 10355 Science Center Drive SAN DIEGO Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato