IVIg suppresses allogeneic mixed lymphocyte reactions by induction of anti-inflammatory monocytes (CD14LOW, HLA-DRHIGH) with CD80LOW and PDL1HIGH expression.

Abstract

Event Abstract Back to Event IVIg suppresses allogeneic mixed lymphocyte reactions by induction of anti-inflammatory monocytes (CD14LOW, HLA-DRHIGH) with CD80LOW and PDL1HIGH expression. Lauriane PADET1, 2* and Renée BAZIN1, 2 1 Héma-Québec, Research and Development, Canada 2 Laval University, Department of Biochemistry, Microbiology and Bioinformatics, Canada Intravenous immunoglobulin (IVIg) is a therapeutic preparation of human IgG isolated from thousands of plasma donations and has been proposed as a therapy to improve the rate of graft survival in patients with a high risk for antibody-mediated-rejection. Blocking of anti-HLA antibodies by anti-idiotypic IgG present in IVIg was proposed to explain the rapid anti-inflammatory effect of IVIg. However, peripheral tolerance beyond the half-life of IVIg was observed in IVIg-treated patients, suggesting that IVIg modulates the functions of immune cells. In the present study we showed, using the allogeneic mixed lymphocyte reaction (MLR) as an in vitro model of allograft rejection and GvHD, that IVIg strongly inhibits IL-2 secretion (T cell activation) and modulates the level of other pro- and anti-inflammatory cytokines secretion (IL-6, INF-γ, TNF-α, IL-1RA). To determine the mechanisms underlying the inhibition of T cell activation in MLR, we studied the effect of IVIg on the phenotype of the cells involved in MLR (mainly T cells and monocytes). Our results revealed that MLR inhibition by IVIg correlates with the induction of anti-inflammatory monocytes (CD14LOW, HLA-DRHIGH) with a low CD80 and high PDL1 expression. To evaluate the importance of PDL1 on the MLR inhibition, anti-PDL1 was added during the MLR. Blocking of PDL1 restored the MLR, as evaluated by IL-2 secretion by activated T cells. We thus propose that PDL1 plays a central role in the inhibition of MLR. Our results help to better understand how IVIg induces long-term peripheral tolerance and improves graft survival in transplanted patients. Keywords: Mixed Lymphocyte Reaction, IVIgG, anti-inflammatory monocytes, PDL1, CD80 Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: PADET L and BAZIN R (2013). IVIg suppresses allogeneic mixed lymphocyte reactions by induction of anti-inflammatory monocytes (CD14LOW, HLA-DRHIGH) with CD80LOW and PDL1HIGH expression.. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00315 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: 18 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Ms. Lauriane PADET, Héma-Québec, Research and Development, Québec, Canada, lauriane.padet@hema-quebec.qc.ca 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 Lauriane PADET Renée BAZIN Google Lauriane PADET Renée BAZIN Google Scholar Lauriane PADET Renée BAZIN PubMed Lauriane PADET Renée BAZIN 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.