International Immunology, Vol. 11, No. 7, 1131-1138,
July 1999
© 1999 Japanese Society for Immunology
Suppressive versus stimulatory effects of allergen/cholera toxoid (CTB) conjugates depending on the nature of the allergen in a murine model of type I allergy
1 Division of Immunopathology, Institute of General and Experimental Pathology, University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria
2 Centre of Ultrastructural Research, University of Agriculture, Vienna, Austria,
3 Department of Microbiology and Immunology, University of Göteborg, Göteborg, Sweden
Correspondence to: U. Wiedermann
Recent reports have demonstrated that feeding small amounts of antigen conjugated to the B subunit of cholera toxin (CTB) suppress immune responses in experimental models of certain Th1-based autoimmune diseases. We have established a model of aerosol sensitization leading to Th2-mediated allergic immune responses in BALB/c mice. In the present study two different antigens, the dietary antigen ovalbumin (OVA) and the inhalant allergen Bet v 1 (the major birch pollen allergen), chemically coupled to recombinant CTB were tested for their potential to influence Th2-like immune responses. Intranasal 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, sensitized animals. Antigen-specific lympho-proliferative responses in vitro were reduced by 65% in the pretreated group; IL-5 and IL-4, but not IFN-
, production were markedly decreased in responder cells of lungs and spleens of nasally pretreated mice. In contrast, mucosal administration of rBet v 1–CTB conjugates prior to sensitization led to an up-regulation of allergen-specific IgE, IgG1 and IgG2a, increased in vitro lympho-proliferative responses as well as augmented production of IL-5, IL-4, IL-10 and IFN-. Intranasal administration prior to sensitization of unconjugated allergens showed also contrasting effects: OVA could not significantly influence antigen-specific antibody or cytokine 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 unconjugated form—had different effects on the Th2 immune responses. We therefore conclude that the tolerogenic or immunogenic properties of CTB—and probably also other antigen-delivery systems—strongly depend on the nature of the coupled antigen–allergen.
Keywords: aerosol, BALB/c, cholera B subunit, intranasal, immunomodulation, Th2 response
Transmitting editor: A. Radbruch
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