Analysis of allergen-specific tolerance induction in patients suffering from type I allergies

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Pollen-allergies are frequently related to food allergies as demonstrated for the birch pollen-food syndrome. Specific immunotherapy, well established for the treatment of pollen-allergies, often failed to affect the associated food allergy and no standard therapeutic approach has been developed so far. In the applied project, we intend to analyse the effect of human tolerogenic DC on the immune response of birch pollen allergics with associated hazelnut allergy. We will use the well-established model of human tolerogenic IL-10-modulated DC to investigate T cell responses induced by Bet v 1 (major allergen of birch) and Cor a 1 (major allergen of hazelnut) loaded tolerogenic DC for the development of an innovative treatment of type I allergies. In our project, we will analyse the induction of regulatory T cells by IL-10DC with focus on the development of suppressor T cells inhibiting both pollen as well as food allergen-specific T cell responses in form of cross-tolerance. In vitro investigation will give insights into the underlying immune mechanisms of the allergen-specific cross-tolerance. In addition, using a humanized model of immunodeficient mice reconstituted with PMBC from allergic patients, we will evaluate the effect of tolerogenic IL-10 DC and iTregs on the resulting T cell response with respect to allergen-specific cross-tolerance in vivo. The results of this study might allow for the development of novel preventive or therapeutic approaches for type I allergies and particularly for pollen-related food allergies.