title: 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.
abstract: 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-gamma, 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-gamma. 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.
authors.affiliation: Division of Immunopathology, Institute of General and Experimental Pathology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: U
authors.initials: U
authors.lastname: Wiedermann
authors.forename: B
authors.initials: B
authors.lastname: Jahn-Schmid
authors.forename: M
authors.initials: M
authors.lastname: Lindblad
authors.forename: C
authors.initials: C
authors.lastname: Rask
authors.forename: J
authors.initials: J
authors.lastname: Holmgren
authors.forename: D
authors.initials: D
authors.lastname: Kraft
authors.forename: C
authors.initials: C
authors.lastname: Ebner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000485:Allergens; D000818:Animals; D052179:Antigens, Plant; D002772:Cholera Toxin; D016207:Cytokines / Q000096:biosynthesis; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D018928:Immunity, Mucosal / Q000276:immunology; D018796:Immunoconjugates / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D010940:Plant Proteins / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014121:Toxoids / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D018796:Immunoconjugates; D015848:Interleukin-5; D010940:Plant Proteins; D014121:Toxoids; C038458:cholera toxoid; C061312:Bet v 1 allergen, Betula; D015847:Interleukin-4; D010047:Ovalbumin; D002772:Cholera Toxin