Event Abstract Back to Event Human regulatory T cells rapidly suppress T cell receptor-induced calcium, NF-κB, and NFAT signaling in conventional T cells Angelika Schmidt1, 2*, Nina Oberle2, Rubin N. Joshi1, Hongying Lin3, Georg W. Mayr3, Stefan Frischbutter4, Ria Baumgrass4, Nadine A. Binai5, Arjen Scholten5, Elisabeth Suri-Payer2, Jesper Tegnér1 and Peter H. Krammer2 1 Karolinska Institutet, Karolinska University Hospital, Department of Medicine, Solna, Sweden 2 German Cancer Research Center (DKFZ), Division of Immunogenetics, Germany 3 University Medical Center Hamburg-Eppendorf, Institut für Biochemie und Signaltransduktion, Germany 4 Deutsches Rheuma-Forschungszentrum (DRFZ), a Leibniz Institute, Germany 5 Utrecht University, Biomolecular Mass Spectrometry and Proteomics group, Netherlands CD4+CD25hiFoxp3+ regulatory T cells (Tregs) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but Tregs can also dampen antitumor immunity. Tregs inhibit the proliferation of CD4+CD25− conventional T cells (Tcons), as well as the ability of these cells to produce effector cytokines; however, the molecular mechanisms of suppression remain incompletely understood. We show that human Tregs rapidly suppressed the release of calcium ions (Ca2+) from intracellular stores in response to T cell receptor (TCR) activation in Tcons. The inhibition of Ca2+ signaling resulted in decreased dephosphorylation, and thus decreased activation, of the transcription factor nuclear factor of activated T cells 1 (NFAT1) and reduced the activation of nuclear factor kB (NF-kB). In contrast, Ca2+-independent events in Tcons, such as TCR-proximal signaling and activation of activator protein 1 (AP-1), were not affected during coculture with Tregs. Despite suppressing intracellular Ca2+ mobilization, coculture with Tregs did not block the generation of inositol 1,4,5-trisphosphate in TCR-stimulated Tcons. The Treg-induced suppression of the activity of NFAT and NF-kB and of the expression of IL-2 was reversed in Tcons by increasing the concentration of intracellular Ca2+. Our results elucidate a previously unrecognized and rapid mechanism of Treg-mediated suppression. Ongoing and future studies aim at deciphering new molecules causative for this rapid suppression by next-generation proteomics studies, pathway analyses and computational data integration. This increased understanding of Treg function and Tcon resistance to suppression may be exploited to generate possible therapies for the treatment of autoimmune diseases and cancer. References Schmidt,A., Oberle,N., Weiß,E.-M., Vobis,D., Frischbutter,S., Baumgrass,R., Falk,C.S., Haag,M., Brügger,B., Lin,H., Mayr,G.W., Reichardt,P., Gunzer,M., Suri-Payer,E., and Krammer,P.H. (2011). Human regulatory T cells rapidly suppress T cell receptor–induced Ca2+, NF-kB, and NFAT signaling in conventional T cells. Sci. Signal. 4, ra90. Keywords: Treg, TCR signaling, regulatory T cells, Calcium, NFAT, NF-kappa B, suppression mechanisms Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune receptors and signaling Citation: Schmidt A, Oberle N, Joshi RN, Lin H, Mayr GW, Frischbutter S, Baumgrass R, Binai NA, Scholten A, Suri-Payer E, Tegnér J and Krammer PH (2013). Human regulatory T cells rapidly suppress T cell receptor-induced calcium, NF-κB, and NFAT signaling in conventional T cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00515 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Angelika Schmidt, Karolinska Institutet, Karolinska University Hospital, Department of Medicine, Solna, Stockholm, Sweden, geli.schmidt@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Angelika Schmidt Nina Oberle Rubin N Joshi Hongying Lin Georg W Mayr Stefan Frischbutter Ria Baumgrass Nadine A Binai Arjen Scholten Elisabeth Suri-Payer Jesper Tegnér Peter H Krammer Google Angelika Schmidt Nina Oberle Rubin N Joshi Hongying Lin Georg W Mayr Stefan Frischbutter Ria Baumgrass Nadine A Binai Arjen Scholten Elisabeth Suri-Payer Jesper Tegnér Peter H Krammer Google Scholar Angelika Schmidt Nina Oberle Rubin N Joshi Hongying Lin Georg W Mayr Stefan Frischbutter Ria Baumgrass Nadine A Binai Arjen Scholten Elisabeth Suri-Payer Jesper Tegnér Peter H Krammer PubMed Angelika Schmidt Nina Oberle Rubin N Joshi Hongying Lin Georg W Mayr Stefan Frischbutter Ria Baumgrass Nadine A Binai Arjen Scholten Elisabeth Suri-Payer Jesper Tegnér Peter H Krammer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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