Modulation of an allergic immune response via the mucosal route in a murine model of inhalative type-I allergy

A murine model of aerosol inhalation, leading to sensitization to birch pol len (BP) and its major allergen Bet v 1, was established in order to try to influence type-1 allergic immune responses via the mucosal route. We previ ously demonstrated that simultaneous inhalation of BP and cholera toxin, a potent mucosal adjuvant, induced a Th1-like immune response to the allergen in naive mice and modulated allergic immune responses in sensitized mice. In contrast to cholera holotoxin, mucosal application of the cholera B subu nit (CTB) conjugated to antigen has been shown to induce peripheral toleran ce in certain models of Th1-based autoimmune diseases. In the present study we investigated the potential of such an antigen delivery system to suppre ss Th2-based, allergic immune responses. Mucosal administration of CTB/Bet v 1 conjugates prior to sensitization led to significantly increased allerg en-specific IgE/IgG1 and IgG2a antibody levels and cytokine production (IL- 5, IFN-gamma) in vitro. Thus, CTB coupled to Bet v 1 acted as an adjuvant r ather than a tolerogen. On the other hand we noted that mucosal application of CTB coupled to ovalbumin led to marked suppression of antigen-specific IgE antibody levels and IL-5 production in vitro and thereby restricted all ergic sensitization. These results indicated that the effects of CTB/antige n conjugates depended on the nature of the antigen. In contrast to Bet v 1 coupled to CTB, nasal as well as oral application of low doses of unconjuga ted, Bet v 1 prior to aerosol sensitization inhibited allergen-specific ant ibody responses of all isotypes, cutaneous type-1 skin tests in vivo as wel l as allergen-specific lymphoproliferative responses and cytokine productio n (IL-4, IL-5, IL-10, IFN-gamma) in vitro, suggesting that both T- and B-ce ll tolerance to the allergen were induced. Taken together, mucosal toleranc e induction as well as the use of certain transmucosal antigen delivery sys tems might be promising new strategies to modulate type-1 allergic immune r esponses.