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.