The Journal of Allergy and Clinical Immunology
Volume 106, Issue 1 , Pages 150-158, July 2000

A murine model of peanut anaphylaxis: T- and B-cell responses to a major peanut allergen mimic human responses☆☆

New York, NY, Baltimore, Md, and Little Rock, Ark

From athe Department of Pediatrics, Mount Sinai School of Medicine, New York; bthe Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore; and cthe Departments of Pediatrics and Biochemistry and Molecular Biology, University of Arkansas, School of Medicine, Little Rock

Received 14 December 1999; received in revised form 23 March 2000; accepted 23 March 2000.

Abstract 

Background: Peanut allergy affects 0.6% of the US population. At the present time, allergen avoidance is the only therapeutic option. Animal models of food-induced anaphylaxis would facilitate attempts to design novel immunotherapeutic strategies for the treatment of peanut allergy. Objective: The purpose of this study was to develop a murine model of IgE-mediated peanut hypersensitivity that closely mimics human peanut allergy. Methods: C3H/HeJ mice sensitized orally with freshly ground whole peanut and cholera toxin as adjuvant were challenged orally 3 and 5 weeks later with crude peanut extract. Anaphylactic reactions were determined. T- and B-cell responses to Ara h 1 and Ara h 2, the major peanut allergens, were characterized by evaluating splenocyte proliferative responses and IgE antibody concentrations. Furthermore, IgE antibodies in the sera of patients with peanut allergy and mice were compared for antibody binding to Ara h 2 isoforms and allergenic epitopes. Results: Peanut-specific IgE was induced by oral peanut sensitization, and hypersensitivity reactions were provoked by feeding peanut to sensitized mice. The symptoms were similar to those seen in human subjects. Ara h 1– and Ara h 2–specific antibodies were present in the sera of mice with peanut allergy. Furthermore, these Ara h 2–specific IgE antibodies bound the same Ara h 2 isoforms and major allergenic epitopes as antibodies in the sera of human subjects with peanut allergy. Splenocytes from mice with peanut allergy exhibited proliferative responses to Ara h 1 and Ara h 2. Conclusion: This murine model of peanut allergy mimics the clinical and immunologic characteristics of peanut allergy in human subjects and should be a useful tool for developing immunotherapeutic approaches for the treatment of peanut allergy. (J Allergy Clin Immunol 2000;106:150-8.)

Keywords:  Peanut anaphylaxis, animal model, B- and T-cell responses

Abbreviations:  CMH , Cow’s milk hypersensitivity, Con A , Concanavalin A, CPE , Crude peanut extract, PBST , PBS containing 0.05% Tween, PCA , Passive cutaneous anaphylaxis, PNA , Peanut allergy, RT , Room temperature, TBST , TRIS-buffered saline containing 1% Tween

 

 Supported by the Clarissa Sosin Allergy Foundation; the Tomich Family and Finkelstein Family Funds; National Institutes of Health grants AI 43668, AI 24439, and AI 33596; and National Institute of Environmental Health Sciences grant ES03819.

☆☆ Reprint requests: Xiu-Min Li, MD, Pediatric Allergy and Immunology, The Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574.

PII: S0091-6749(00)28755-1

doi:10.1067/mai.2000.107395

The Journal of Allergy and Clinical Immunology
Volume 106, Issue 1 , Pages 150-158, July 2000