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Title
Cell Therapy for Prophylactic Tolerance in Immunoglobulin E-mediated Allergy
AuthorWekerle, Thomas ; Valenta, Rudolf In der Gemeinsamen Normdatei der DNB nachschlagen ; Ruelicke, Thomas ; Wrba, Fritz ; Petersen, Arnd ; Focke-Tejkl, Margit ; Gattringer, Martina ; Linhart, Birgit ; Mahr, Benedikt ; Hock, Karin ; Farkas, Andreas M. ; Baranyi, Ulrike
Published in
EBioMedicine, Amsterdam, 2016, Vol. 7, page 230-239
PublishedAmsterdam : Elsevier, 2016
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Publisher version
LanguageEnglish
Document typeJournal Article
Keywords (EN)allergy prophylaxis / cell-based therapy / b-cell tolerance / t-cell tolerance / allergen-specific tolerance induction / regulatory t-cells / hematopoietic stem-cells / mixed chimerism / in-vivo / b-cells / pronuclear microinjection / transplantation tolerance / costimulation blockade / antigen presentation / airway inflammation
Project-/ReportnumberW 1212-B21
ISSN2352-3964
URNurn:nbn:at:at-ubmuw:3-1363 Persistent Identifier (URN)
DOI10.1016/j.ebiom.2016.03.028 
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Abstract (English)

Background: Therapeutic strategies for the prophylaxis of IgE-mediated allergy remain an unmet medical need. Cell therapy is an emerging approach with high potential for preventing and treating immunological diseases. We aimed to develop a cell-based therapy inducing permanent allergen-specific immunological tolerance for preventing IgE-mediated allergy. Methods: Wild-type mice were treated with allergen-expressing bone marrow cells under a short course of tolerogenic immunosuppression (mTOR inhibition and costimulation blockade). Bone marrow was retrieved from a novel transgenic mouse ubiquitously expressing the major grass pollen allergen Phl p 5 as a membrane-anchored protein (BALB/c-Tg[Ph1p5-GFP], here mPhl p 5). After transplantation recipients were lgE-sensitized at multiple time points with Phl p 5 and control allergen. Results: Mice treated with mPhl p 5 bone marrow did not develop Phl p 5-specific IgE (or other isotypes) despite repeated administration of the allergen, while mounting and maintaining a strong humoral response towards the control allergen. Notably, Phl p 5-specific T cell responses and allergic airway inflammation were also completely prevented. interestingly allergen-specific B cell tolerance was maintained independent of Treg functions indicating deletional tolerance as underlying mechanism. Conclusion: This proof-of-concept study demonstrates that allergen-specific immunological tolerance preventing occurrence of allergy can be established through a cell-based therapy employing allergen-expressing leukocytes. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.orgilicenses/by-nc-nd/4.0/).

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CC-BY-NC-ND-License (4.0)Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License