Int Immunol. 1999 Jul;11(7):1131-8. Unique Identifier : AIDSLINE
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.
JOURNAL ARTICLE Adjuvants, Immunologic/*ADMINISTRATION & DOSAGE
Administration, Intranasal Animal Comparative Study
Cytokines/BIOSYNTHESIS *Desensitization, Immunologic Disease Models,
Animal Female Hypersensitivity,
Immediate/*IMMUNOLOGY/METABOLISM/THERAPY Immunity, Mucosal/IMMUNOLOGY
Immunoconjugates/*IMMUNOLOGY Interleukin-4/BIOSYNTHESIS
Interleukin-5/BIOSYNTHESIS Lymphocyte Transformation/IMMUNOLOGY Mice
Mice, Inbred BALB C Ovalbumin/*IMMUNOLOGY Plant Proteins/*IMMUNOLOGY
Support, Non-U.S. Gov't Th2 Cells/IMMUNOLOGY Toxoids/*IMMUNOLOGY