Abstract
BackgroundOur previous studies on intranasal tolerance induction demonstrated reduction of allergic responses with different allergen constructs. The underlying mechanisms varied depending on their conformation or size.ObjectiveThe aim of the present study was to compare the uptake of two structurally different allergen molecules within the respiratory tract following intranasal application.MethodsThe three-dimensional Bet v 1 (Bv1-Protein) and the T cell epitope peptide of Bet v 1 (Bv1-Peptide) were labelled with 5,6-Carboxyfluorescein (FAM) and their uptake was investigated in lung cells and cells of the nasal associated lymphoid tissue from naive and sensitised BALB/c mice. Phenotypic characterisation of FAM+ lung cells after antigen incubation in vitro and after intranasal application was performed by flow cytometry. Impact of Bv1-Protein and Bv1-Peptide on cytokine profiles and gene expression in vivo or in an alveolar epithelial type II (ATII) cell line were assessed in mono- and co-cultures with monocytes using ELISA and quantitative real-time PCR.ResultsBoth antigens were taken up preferably by ATII-like cells (ATII-LCs) in naive mice, and by macrophages in sensitised mice. After intranasal application, Bv1-Peptide was taken up faster and more efficiently than Bv1-Protein. In vivo and in vitro experiments revealed that Bv1-Protein induced the transcription of thymic stromal lymphopoietin mRNA while Bv1-Peptide induced the transcription of IL-10 and MCP1 mRNA in ATII-LCs.Conclusion and Clinical RelevanceBoth tested antigens were taken up by ATII-LCs under steady state conditions and induced different polarisation of the immune responses. These data may have an important impact for the generation of novel and more effective prophylactic or therapeutic tools targeting the respiratory mucosa.
Highlights
Type I allergic disorders such as allergic rhinitis, asthma, and atopic eczema are affecting ~20% of westernised countries [1,2]
Bv1-Protein induced the transcription of thymic stromal lymphopoietin mRNA while Bv1Peptide induced the transcription of IL-10 and MCP1 mRNA in alveolar epithelial type II (ATII)-LCs
Lung cells derived from naive BALB/c mice were incubated with 5 μg/ml of FAM-labelled Bv1-Protein or Bv1-Peptide for different time points (0.5–48 hours)
Summary
Type I allergic disorders such as allergic rhinitis, asthma, and atopic eczema are affecting ~20% of westernised countries [1,2]. In allergy-prone patients, this contact results in T helper type 2-skewed (TH2) immune response leading to IgE-mediated clinical manifestations. The only immune modifying and potentially curative treatment for type I allergy is allergen-specific immunotherapy (SIT). The goal of SIT is to generate a switch from allergen-specific T cells to tolerant or anergic T cells and down regulation of IgE-mediated immune responses in allergic patients [3]. In order to increase the safety of SIT, we and others have generated recombinant allergens, non-IgE binding T cell epitopes, polypeptide constructs, or fragments of the allergens without IgE reactivity [5,6,7,8] and tested their efficacy in different mouse models of type I allergy [4]. The underlying mechanisms varied depending on their conformation or size
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