Background: The major birch pollen allergen Bet v 1 represents one of the most prevalent environmental allergens responsible for allergic airway inflammation. Objective: In the present study we sought to compare the complete recombinant Bet v 1 allergen molecule with genetically produced hypoallergenic fragments of Bet v 1 regarding mucosal tolerance induction in a mouse model of allergic asthma. Methods: BALB/c mice were intranasally treated with recombinant Bet v 1 or with two recombinant Bet v 1 fragments (F I: aa 1–74; F II: aa 75–160) prior to aerosol sensitization with birch pollen and Bet v 1. Results: Intranasal application of F II, containing the major T cell epitope, led to significant reduction of IgE/IgG1 antibody responses, in vitro cytokine production (IL-5, IFN-γ, IL-10) and negative immediate cutaneous hypersensitivity reactions comparable to the pretreatment with the complete rBet v 1 allergen. Moreover, airway inflammation (eosinophilia, IL-5) was inhibited by the pretreatment with either the complete Bet v 1 or F II. However, for prevention of airway hyperresponsiveness the complete molecule was required. The mechanisms leading to immunosuppression seemed to differ in their dependence on the conformation of the molecules, since tolerance induced with the complete Bet v 1, but not with F II, was transferable with spleen cells and associated with increased TGF-β mRNA levels. Conclusion: We conclude that mucosal tolerance induction with recombinant allergens and genetically engineered hypoallergenic derivatives thereof could provide a convenient and safe intervention strategy against type I allergy.
Background Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the ef®cacy of mucosal tolerance for therapy of such diseases. Objective The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism. Methods A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavagē uids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)-5, interferon (IFN)-g) were measured in spleen and lung cell cultures.Results Mucosal treatment with rBet v 1 (3 Â 50 mg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-g production in vitro in spleen and lung cell cultures. Moreover, lung in¯ammation (i.e. eosinophilia and IL-5 levels in bronchoalveolar lavage¯uids) was signi®cantly suppressed by the treatment. Conclusion Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway in¯ammation in BP-sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.
Taking these results together, our data indicate that Bet mim 1 mimics a Bet v 1-epitope on the B cell but not on the T cell level. We suggest that the phage itself is responsible for the recruitment of T cells providing bystander help in the formation of a mimotope-specific humoral response.
SUMMARYThe prevalence of type I allergy to Hevea brasiliensis latex is particularly high among individuals with frequent exposure to latex products, such as health-care workers (HCW) and patients with spina bifida (SB). Treatment of latex allergy seems problematic as preventive measures, such as allergen avoidance, are not always possible and conventional immunotherapy with standardized latex extracts is not performed routinely. Thus, the aim of the present study was to establish a mouse model of latex allergy using two major latex allergens for HCWs and SB patients, Hev b 1 and Hev b 3, for sensitization. Prophylactic measures on the basis of mucosal tolerance induction with the recombinant allergens were tested in this model. Female BALB/c mice immunized intraperitoneally with recombinant (r)Hev b 1 or rHev b 3 displayed strong immune responses in vivo and in vitro . Intranasal treatment with rHev b 1 and rHev b 3 prior to sensitization led to reduced allergen-specific IgG1/IgE levels and significantly suppressed allergen-induced basophil degranulation. Moreover, lymphocyte proliferation and cytokine production (IL-4, IL-5, IFN-g ) in vitro were significantly suppressed after pretreatment with both allergens. Suppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-b , remained unchanged after the intranasal pretreatment, indicating mechanism of anergy rather than active immunosuppression. Taken together, these results suggest that mucosal tolerance induction with recombinant allergens could present a promising prevention strategy against latex allergy.
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