Mixed antibody and T cell responses to peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 in an oral sensitization model.
BACKGROUND
Peanut allergy is known for its severity and persistence through life. Several peanut proteins have been identified as allergenic and are indicated as Ara h 1-7. Very little is known about the mechanisms that underlie sensitization to peanut proteins.


OBJECTIVE
The purpose of the present study was to reveal the immune responses that are induced against peanut and the peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 during sensitization, including the very early responses.


METHODS
Humoral and T cell responses against peanut and the peanut allergens were examined in an early and later stage of sensitization in an established murine model of peanut anaphylaxis. Therefore C3H/HeJ mice were orally exposed to two different doses of peanut extract plus cholera toxin.


RESULTS
Oral sensitization to peanut was characterized by an antigen-induced mixed cytokine response in the spleen (IL-4, IL-5, IL-10 and IFN-gamma), which could already be observed 7 days after the onset of exposure. Additionally, polyisotypic humoral responses (IgE, IgG1 and IgG2a) against peanut were found in the serum. Moreover, we demonstrated that these T helper (Th)1/Th2 cytokine and antibody responses were also directed specifically against the major peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6.


CONCLUSIONS
This study implicates that both Th1 and Th2 phenomena are involved in the development of peanut allergy in the C3H/HeJ murine model. Furthermore, we show that the present oral model is suitable to examine immune responses to food allergens during different stages of sensitization upon treatment with a whole food extract.
van Wijk
F
F
Institute for Risk Assessment Sciences, Immunotoxicology, Utrecht University, Utrecht, The Netherlands.
Hartgring
S
S
Koppelman
S J
SJ
Pieters
R
R
Knippels
L M J
LM
D055516:2S Albumins, Plant; D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D010367:Arachis / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D021183:Peanut Hypersensitivity / Q000276:immunology*; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D055516:2S Albumins, Plant; D000485:Allergens; D052179:Antigens, Plant; C500889:Ara h 1 protein, Arachis hypogaea; C492737:Ara h 6 allergen, Arachis hypogaea; C078642:Ara h II protein, Arachis hypogaea; D016207:Cytokines; D006023:Glycoproteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007136:Immunoglobulins; D008565:Membrane Proteins; D010940:Plant Proteins; D007073:Immunoglobulin E