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.
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 T(h)1-based autoimmune diseases. We have established a model of aerosol sensitization leading to T(h)2-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 T(h)2-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 production were 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 T(h)2 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.
Wiedermann
U
U
Division of Immunopathology, Institute of General and Experimental Pathology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Jahn-Schmid
B
B
Lindblad
M
M
Rask
C
C
Holmgren
J
J
Kraft
D
D
Ebner
C
C
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D002772:Cholera Toxin; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D007108:Immune Tolerance; D018928:Immunity, Mucosal / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000032:analysis; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000378:metabolism; D014121:Toxoids / Q000008:administration & dosage / Q000276:immunology*
D000485:Allergens; D007074:Immunoglobulin G; D007378:Interleukins; D010940:Plant Proteins; D014121:Toxoids; C038458:cholera toxoid; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D002772:Cholera Toxin