Objectif The immune response is a potent defensive reaction within the organism that can lead to deleterious self-damaging effects in absence of control mechanisms. The modulation of the immune response is exerted at many different levels including T cell-mediated immuno-regulation. Regulatory T cells (TR cells) have recently been identified which have the capacity to control the activity of effectors T cells. Operationally, TR cells are defined by the ability to suppress the expansion of pathogenic naive T cells in vitro and to inhibit inflammatory reactions in mouse experimental systems. However, the mechanisms by which TR cells mediate immune-regulatory events are poorly described. In fact, it is not known whether this TR cell mediated suppression requires a direct cell-to-cell contact between TR cells, Antigen Presenting Cells (APCs) and target Tcells. Furthermore, the stochiometry of the cellular interactions, the dynamics of such interactions and the site(s) of in vivoimmune regulation are largely unknown. The aim of this project is to characterise the cellular interactions occurring during immune regulation events in vitro using the suppression assay system, and in vivo by analysing intact organs of different animal models of immune regulation. Conventional and multi-photon confocal microscopy will be applied to visualise invitro and in vivo interactions of APCs with CD4+CD25+ TR cells and naïve (effector) T cells previously sorted by flowcytometry, from Yellow Fluorescent Protein and Cyan Fluorescent Protein transgenic mice, respectively. These experiments will be designed to assess (1) whether CD4+CD25+ TR cells suppress naïve T cells by direct interaction or through an indirect effect via APCs, (2) whether the CD4+CD25+ TR cell-mediated immune regulation occurs at the site of tissue inflammation or in draining lymph nodes and (3) whether the kinetics of cell migration to the sites of immune regulation and tissue inflammation. Champ scientifique medical and health sciencesbasic medicineimmunologyimmunisationnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyconfocal microscopy Mots‑clés Immune responses T lymphocytes confocal microscopy immune regulation in vivo imaging transgenic Programme(s) 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 Thème(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Appel à propositions FP6-2002-MOBILITY-5 Voir d’autres projets de cet appel Régime de financement EIF - Marie Curie actions-Intra-European Fellowships Coordinateur FUNDACAO CALOUSTE GULBENKIAN Contribution de l’UE Aucune donnée Adresse Av.Berna 45A LISBOA Portugal Voir sur la carte Coût total Aucune donnée
