Cell Therapy for Prophylactic Tolerance in Immunoglobulin E-mediated Allergy

• Main Authors: Ulrike Baranyi, Andreas M. Farkas, Karin Hock, Benedikt Mahr, Birgit Linhart, Martina Gattringer, Margit Focke-Tejkl, Arnd Petersen, Fritz Wrba, Thomas Rülicke, Rudolf Valenta, Thomas Wekerle
• Format: Article
• Language: English
• Published: Elsevier 2016-05-01
• Series: EBioMedicine
• Subjects: Allergy prophylaxis; Cell-based therapy; B-cell tolerance; T-cell tolerance; Allergen-specific tolerance induction
• Online Access: http://www.sciencedirect.com/science/article/pii/S2352396416301141

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[Phlp5-GFP], here mPhl p 5). After transplantation recipients were IgE-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.