IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis

Abstract

Event Abstract Back to Event IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis Magdalena Huber1*, Sylvia Heink2, Axel Pagenstecher3, Katharina Reinhard1, Josephine Ritter1, Alexander Visekruna1, Anna Guralnik1, Thomas Kamradt2 and Michael Lohoff1 1 Institute for Medical Microbiology and Hygiene, University of Marburg, Germany 2 Jena University Hospital, Institute for Immunology, Germany 3 University of Marburg, Department for Neuropathology, Germany IL-17-producing CD8+ T (Tc17) cells are detectible in multiple sclerosis (MS) lesions; however their contribution to the disease is unknown. To identify functions of Tc17 cells, we induced experimental autoimmune encephalitis (EAE), a murine model of MS, in mice lacking interferon regulatory factor 4 (IRF4). IRF4-deficient mice failed to generate Tc17 and Th17 cells and were resistant to EAE. After adoptive transfer of wild-type CD8+ T cells and subsequent immunization for EAE induction in these mice, the CD8+ T cells developed a Tc17 phenotype in the periphery but could not infiltrate the CNS. Similarly, transfer of small numbers of wild-type CD4+ T cells alone did not evoke EAE, but when transferred together with CD8+ T cells, IL-17-producing CD4+ (Th17) T cells accumulated in the CNS and mice developed severe disease. Th17 accumulation and development of EAE required IL-17A production by CD8+ T cells, suggesting that Tc17 cells are required to promote CD4+ T cell-mediated induction of EAE. Accordingly, patients with early-stage MS harbored a greater number of Tc17 cells in the cerebrospinal fluid than in peripheral blood. Our results reveal that Tc17 cells contribute to the initiation of CNS autoimmunity in mice and humans by supporting Th17-cell pathogenicity. References J. Clin. Invest. doi:10.1172/JCI63681 Keywords: Th17, Tc17, Autoimmunity, Encephalomyelitis, EAE Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Huber M, Heink S, Pagenstecher A, Reinhard K, Ritter J, Visekruna A, Guralnik A, Kamradt T and Lohoff M (2013). IL-17A secretion by CD8+ T cells supports Th17-mediated autoimmune encephalomyelitis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00939 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: 25 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Magdalena Huber, Institute for Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany, magdalena.huber@staff.uni-marburg.de 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 Magdalena Huber Sylvia Heink Axel Pagenstecher Katharina Reinhard Josephine Ritter Alexander Visekruna Anna Guralnik Thomas Kamradt Michael Lohoff Google Magdalena Huber Sylvia Heink Axel Pagenstecher Katharina Reinhard Josephine Ritter Alexander Visekruna Anna Guralnik Thomas Kamradt Michael Lohoff Google Scholar Magdalena Huber Sylvia Heink Axel Pagenstecher Katharina Reinhard Josephine Ritter Alexander Visekruna Anna Guralnik Thomas Kamradt Michael Lohoff PubMed Magdalena Huber Sylvia Heink Axel Pagenstecher Katharina Reinhard Josephine Ritter Alexander Visekruna Anna Guralnik Thomas Kamradt Michael Lohoff 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.