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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

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Author: Wijk, F. van · Hartgring, S. · Koppelman, S.J. · Pieters, R. · Knippels, L.M.J.
Type:article
Date:2004
Institution: TNO Voeding
Source:Clinical and Experimental Allergy, 9, 34, 1422-1428
Identifier: 237962
doi: doi:10.1111/j.1365-2222.2004.02062.x
Keywords: Biology · Food technology · Cytokines · Oral mouse model · Peanut allergens · Peanut hyper-sensitivity · Sensitization · Th1/Th2 responses · antibody · cholera toxin · cytokine · food allergen · gamma interferon · immunoglobulin E · immunoglobulin G1 · immunoglobulin G2a · interleukin 10 · interleukin 4 · interleukin 5 · protein Ara h 1 · protein Ara h 2 · protein Ara h 3 · protein Ara h 6 · unclassified drug · anaphylaxis · animal cell · animal experiment · animal model · antibody detection · antibody response · article · controlled study · cytokine production · disease model · exposure · female · humoral immunity · immune response · mouse · nonhuman · peanut · peanut allergy · priority journal · sensitization · serum · spleen · T lymphocyte · Th1 cell · Th2 cell · Administration, Oral · Allergens · Animals · Arachis hypogaea · Cells, Cultured · Cytokines · Disease Models, Animal · Female · Glycoproteins · Immunoglobulin A · Immunoglobulin E · Immunoglobulin G · Immunoglobulins · Mice · Mice, Inbred C3H · Peanut Hypersensitivity · Plant Proteins · Spleen · T-Lymphocytes, Helper-Inducer · Th1 Cells · Th2 Cells

Abstract

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-γ), 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.