Innate memory CD4+ T cells suppress autoimmune graft-versus-host disease

Abstract

Event Abstract Back to Event Innate memory CD4+ T cells suppress autoimmune graft-versus-host disease Weishan Huang1, 2, Jianfang Hu2, Qian Qi1, 2, Fei Huang1, 2, Terri M. Laufer3 and Avery August1, 2* 1 Cornell University, Department of Microbiology & Immunology and Infection & Pathobiology Program, United States 2 The Pennsylvania State University, Huck Institutes of Life Sciences and Center for Molecular Immunology and Infectious Disease, United States 3 University of Pennsylvania School of Medicine, Department of Medicine, United States Chronic graft-versus-host disease (cGVHD) is the major complication post hematopoietic cell transplantation. Major histocompatibility complex class II (MHCII) mediated CD4+ T cell differentiation and function plays a critical role in cGVHD, and the lack of hematopoietic MHCII (H-MHCII) causes cGVHD in syngeneic irradiated murine recipients. We have studied this process using murine bone marrow transplant of MHCII deficient or sufficient donors. We find that irradiated WT recipients that received MHCII-/- bone marrow exhibited a systemic decrease in IL-10 and increase in TNF-α production, and defective development of H-MHCII dependent innate memory phenotype (IMP, CD44hi/CD62Llo) CD4+ T cells. Transfer of IMP CD4+ T cells, but not conventional regulatory T cells, abrogate the pathogenesis and suppress the activation of pro-inflammatory intraepithelial lymphocytes. The presence of MHCII on dendritic cells (DCs) is sufficient to rescue IMP CD4+ T cell development and reverse subsequent pathogenesis. Furthermore, the absence of the Tec kinase ITK rescues the development of IMP CD4+ T cells independent of MHCII expression on donor bone marrow, and resultant Itk-/- IMP CD4+ cells can partially prevent the pathogenesis. We conclude that IMP CD4+ T cells can act as a suppressive population during cGVHD, and that DC expression of MHCII is critical for the development of such IMP CD4+ T cells. In addition, ITK regulates the development of IMP CD4+ T cells partially independent of DC expression of MHCII. This work provides a mechanism for the development of cGVHD, and suggests an approach of suppressing such responses in syngeneic bone marrow graft. Acknowledgements We thank Shailaja Hegde, Nicole Bem, Susan Magargee, Lavanya G. Sayam, Gabriel Balmus, Jennifer D. Mosher, Yuting Bai, Tina Chew, Dr. Rod Getchell and Dr. Walter Iddings for technical assistance. We also thank Margaret Potter and Amie Wood for animal care. This work was supported by grants from the National Institutes of Health (AI051626 and AI065566 to A.A.). Keywords: dendritic cell, graft-versus-host disease, Innate Memory CD4+ T cells, MHC class II, IL-2 inducible T cell kinase Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Huang W, Hu J, Qi Q, Huang F, Laufer TM and August A (2013). Innate memory CD4+ T cells suppress autoimmune graft-versus-host disease. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00075 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: 08 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Avery August, Cornell University, Department of Microbiology & Immunology and Infection & Pathobiology Program, Ithaca, New York, 14853, United States, averyaugust@cornell.edu 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 Weishan Huang Jianfang Hu Qian Qi Fei Huang Terri M Laufer Avery August Google Weishan Huang Jianfang Hu Qian Qi Fei Huang Terri M Laufer Avery August Google Scholar Weishan Huang Jianfang Hu Qian Qi Fei Huang Terri M Laufer Avery August PubMed Weishan Huang Jianfang Hu Qian Qi Fei Huang Terri M Laufer Avery August 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.