Experimental parameters differentially affect the humoral response of the cholera-toxin-based murine model of food allergy.
BACKGROUND
Recent studies have developed a murine model of IgE-mediated food allergy based on oral coadministration of antigen and cholera toxin (CT) to establish a maximal response for studying immunopathogenic mechanisms and immunotherapeutic strategies. However, for studying subtle immunomodulating factors or factors effective during response initiation, this maximal response-based model is less suitable due to a lack of sensitivity. Therefore, in attempts to identify essential parameters to fine-tune the immune response towards a submaximal level, potentially more sensitive, we were interested in characterizing the individual effects of the parameters in the CT-based model: CT dose, antigen type and dose, and number of immunizations.


METHODS
BALB/c mice were orally sensitized weekly for 3 or 7 weeks with graded doses of CT and various food antigens (soy-trypsin inhibitor, ovalbumin or ovomucoid). Antigen-specific IgG1, IgG2a, IgA and IgE were monitored by ELISA.


RESULTS
The CT dose exerted a clear dose-dependent effect on the antigen-specific antibody response whereas the antigen dose tended to affect the kinetics of the developing response. Both the intensity and kinetics of the antibody response depended on the type of antigen and number of immunizations.


CONCLUSIONS
The critical parameters of the CT-based murine allergy model differentially control the intensity and kinetics of the developing immune response. Adjustment of these parameters could be a key tool for tailoring the response to submaximal levels rendering the model potentially more sensitive for evaluating the effect of subtle immunomodulating factors that would be lost in the maximal response-based model.
Kroghsbo
Stine
S
BioCentrum-DTU, Biochemistry and Nutrition, Technical University of Denmark, Lyngby, Denmark.
Christensen
Hanne Risager
HR
Frøkiaer
Hanne
H
D000818:Animals; D002772:Cholera Toxin / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology*; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010059:Ovomucin / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000276:immunology
D010059:Ovomucin; D007073:Immunoglobulin E; D010047:Ovalbumin; D002772:Cholera Toxin; D014360:Trypsin Inhibitor, Kunitz Soybean