Suppressive versus stimulatory effects of allergen/cholera toroid (CTB) conjugates depending on the nature of the allergen in a murine model of type I allergy (vol. 11, pg. 1131, 1999)

Recent reports have demonstrated that feeding small amounts of antigen conj ugated to the B subunit of cholera toxin (CTB) suppress immune responses in experimental models of certain T(h)1-based autoimmune diseases. We have es tablished a model of aerosol sensitization leading to T(h)2-mediated allerg ic immune responses in BALB/c mice. In the present study two different anti gens, the dietary antigen ovalbumin (OVA) and the inhalant allergen Bet v 1 (the major birch pollen allergen), chemically coupled to recombinant CTB w ere tested for their potential to influence T(h)2-like immune responses, In tranasal administration of OVA-CTB prior to sensitization with OVA led to a significant decrease of antigen-specific IgE antibody levels, but a marked increase of OVA-specific IgG2a antibodies as compared to non-pretreated, s ensitized animals. Antigen-specific lympho-proliferative responses in vitro were reduced by 65% in the pretreated group; IL-5 and IL-4 production were decreased in responder cells of lungs and spleens of nasally pretreated mi ce, In contrast, mucosal administration of rBet v 1-CTB conjugates prior to sensitization led to an upregulation of allergen-specific IgE, IgG1 and Ig G2a, increased in vitro lympho-proliferative responses as well as augmented production of IL-5, IL-4, IL-10 and IFN-gamma, Intranasal administration p rior to sensitization of unconjugated allergens showed also contrasting eff ects: OVA could not significantly influence antigen-specific antibody or cy tokine production, whereas intranasal pretreatment with unconjugated Bet v 1 suppressed allergen-specific immune responses in vivo and in vitro. These results demonstrated that the two antigens-in conjugated as in unconjugate d form-had different effects on the T(h)2 immune responses. We therefore co nclude that the tolerogenic or immunogenic properties of CTB-and probably a lso other antigen-delivery systems-strongly depend on the nature of the cou pled antigen-allergen.