Human conventional CD1c+ Dendritic Cells produce IL-12 and induce potent CD8+ T cell priming

Abstract

Event Abstract Back to Event Human conventional CD1c+ Dendritic Cells produce IL-12 and induce potent CD8+ T cell priming Giulia Nizzoli1, Anja Weick2, Jana Krietsch2, Svenja Steinfelder2, Federica Facciotti1, Sergio Abrignani1 and Jens Geginat1* 1 INGM, Italy 2 DRFZ, Germany BDCA-3+ dendritic cells are thought to be the human equivalents of murine CD8α+ DC, which cross-prime CD8+ T-cell responses and secrete high amounts of IL-12. We compared human myeloid DC expressing CD1c or BDCA-3 and plasmacytoid DC for cytokine production and surface receptor expression in peripheral blood and lymphoid tissues, and assessed their capacities to induce cytotoxic T cell responses. We found that mDC1, but not other DC or monocyte subsets could secrete high amounts of IL-12p70. IL-12 production by mDC1 was tightly controlled, as it required combinational Toll-like receptor (TLR) stimulation and was fine-tuned by lymphocyte-derived stimuli. Conversely, mDC2 produced high levels of IFNlambda in response to TLR-3 stimulation alone. pDC secreted IFNalpha  expressed lower levels of MHC class-I and -II, CD40 and CD86 than myeloid DC. Moreover, they poorly cross-presented soluble antigens to CD8+ T cells. In contrast, both mDC1 and mDC2 could cross-present efficiently, but required different combinations of TLR ligands. Nevertheless, all DC subsets induced secondary expansions of CD8+ memory T-cells upon licensing by CD4+ T-cells. Furthermore, following appropriate TLR stimulation and help by CD4+ T cells, all DC primed naive CD8+ T-cells. However, while mDC1 induced high levels of Granzyme B via IL-12, mDC2 and pDC induced preferentially Granzyme A. Our results show that CD1c+ mDC1 are a relevant source of IL-12 for naïve T cell priming, and that specific pathogen-derived stimuli and CD4 help can instruct different DC subsets to induce cytotoxic T-cell responses. Keywords: human DC subsets, IL-12p70, cross-presentation, CD8+ priming, MDC1 Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Nizzoli G, Weick A, Krietsch J, Steinfelder S, Facciotti F, Abrignani S and Geginat J (2013). Human conventional CD1c+ Dendritic Cells produce IL-12 and induce potent CD8+ T cell priming. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00876 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: 21 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Jens Geginat, INGM, Milano, Italy, geginat@ingm.org 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 Giulia Nizzoli Anja Weick Jana Krietsch Svenja Steinfelder Federica Facciotti Sergio Abrignani Jens Geginat Google Giulia Nizzoli Anja Weick Jana Krietsch Svenja Steinfelder Federica Facciotti Sergio Abrignani Jens Geginat Google Scholar Giulia Nizzoli Anja Weick Jana Krietsch Svenja Steinfelder Federica Facciotti Sergio Abrignani Jens Geginat PubMed Giulia Nizzoli Anja Weick Jana Krietsch Svenja Steinfelder Federica Facciotti Sergio Abrignani Jens Geginat Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.