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

花粉过敏通常与食物过敏有关，如桦树花粉食物综合征。特异性免疫疗法，为花粉过敏症的治疗建立良好，往往未能影响相关的食物过敏症，迄今为止还没有标准的治疗方法。在应用项目中，我们打算分析人致耐受性DC对桦树花粉过敏症伴榛子过敏症的免疫应答的影响。我们将使用完善的人致耐受性IL-10调节的DC模型来研究由Bet v 1（桦树的主要过敏原）和Cor a 1（榛子的主要过敏原）负载的致耐受性DC诱导的T细胞应答，以开发I型过敏的创新治疗。在我们的项目中，我们将分析IL-10 DC对调节性T细胞的诱导，重点是抑制性T细胞的发展，抑制花粉以及食物过敏原特异性T细胞反应的交叉耐受性。体外研究有助于深入了解过敏原特异性交叉耐受的免疫机制。此外，使用用来自过敏性患者的PMBC重建的免疫缺陷小鼠的人源化模型，我们将评估致耐受性IL-10 DC和iTlR对所产生的T细胞应答关于体内过敏原特异性交叉耐受的作用。这项研究的结果可能有助于开发新的预防或治疗I型过敏的方法，特别是花粉相关的食物过敏。

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.