Suppression of antigen-specific T- and B-cell responses by intranasal or oral administration of recombinant Bet v 1, the major birch pollen allergen, in a murine model of type I allergy

Abstract

Background: Mucosal (nasal or oral) administration of soluble protein antigens induces a state of antigen-specific immunologic hyporesponsiveness. Several studies have shown that induction of mucosal tolerance can prevent the onset or reduce the severity of certain T H1 -mediated experimental autoimmune diseases. Only a few studies describe similar results for type I allergies, which are caused by excessive T H2 cell activities. Objective: We sought to investigate whether mucosal tolerance induction would also be efficient in preventing an allergic type I immune response. Methods: A murine model of inhalative type I allergy, leading to sensitization to birch pollen and its major allergen Bet v 1 in BALB/c mice, was used. Recombinant Bet v 1 was nasally or orally applied in low doses before sensitization. At the time of death, immediate-type skin tests were performed. Blood was taken, and serum was used for measurement of allergen-specific antibodies. Spleen cell cultures were performed to determine cytokine production (IL-4, IL-5, IL-10, and IFN-γ), as well as levels of TGF-β mRNA. Results: Both nasal and oral administration of minimal doses of recombinant Bet v 1 before aerosol sensitization with birch pollen suppressed the allergen-specific antibody production of all isotypes. Consequently, the in vivo type I skin test responses to the allergen were negative in the tolerized, in contrast to the sensitized, group. Moreover, allergen-specific lymphoproliferative responses and cytokine production in vitro (ie, IFN-γ, IL-4, IL-5, and IL-10) were markedly reduced. In contrast, expression of TGF-β mRNA was markedly increased in spleen cells from nasally tolerized animals, indicating regulatory mechanisms for tolerance induction. Conclusion: We conclude from the present study that nasal, as well as oral, administration of recombinant allergen is an effective way to prevent allergen-specific T- and B-cell responses in a T H2 model. (J Allergy Clin Immunol 1999;103:1202-10.)