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* Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine and
Department of Medicine, McMaster University, Hamilton, Ontario, Canada; and
Department of Inflammation and Autoimmunity, MedImmune, Gaithersburg, MD 20878
The effector immune mechanisms underlying peanut-induced anaphylaxis remain to be fully elucidated. We investigated the relative contribution of Igs, mast cells (MCs), and Fc
RI in the elicitation of anaphylaxis in a murine model. Assessment of peanut hypersensitivity reactions was performed clinically and biologically. Our data show that wild-type (WT; C57BL/6 strain) mice consistently developed severe anaphylaxis (median clinical score: 3.5/5), an 
8°C drop in core body temperature, and significantly increased plasma levels of histamine and leukotrienes. CD40 ligand- and B cell-deficient mice presented evidence of allergic sensitization as demonstrated by production of Th2-associated cytokines by splenocytes and a late-phase inflammatory response that were both indistinguishable to those detected in WT mice. However, CD40 ligand- and B cell-deficient mice did not exhibit any evidence of anaphylaxis. Our data also show that MC-deficient (KitW/KitW-v) mice did not suffer, unlike their littermate controls, anaphylactic reactions despite the fact that serum levels of peanut-specific Igs were similarly elevated. Finally, FcRI-deficient mice experienced anaphylactic responses although to a significantly lesser degree than those observed in WT mice. Thus, these data demonstrate that the presence of peanut-specific Abs along with functional MCs comprise a necessary and sufficient condition for the elicitation of peanut-induced anaphylaxis. That the absence of FcRI prevented the development of anaphylaxis only partially insinuates the contribution of an IgE-independent pathway, and suggests that strategies to impair MC degranulation may be necessary to improve the efficacy of anti-IgE therapy.
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1 This work was supported by the Food Allergy Initiative organization (New York, NY). M.J. holds a Senior Canada Research Chair on the Immunology of Respiratory Disease and Allergy. D.A. and R.F. held Canadian Institutes of Health Research Doctoral Awards.
2 J.S. and K.A. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Manel Jordana, Department of Pathology and Molecular Medicine and Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, Michael G. DeGroote Centre for Learning and Discovery, Room 4013, McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada. E-mail address: jordanam{at}mcmaster.ca
4 Abbreviations used in this paper: PA, peanut allergy; PIA, peanut-induced anaphylaxis; CD40L, CD40 ligand; PP, peanut protein; PL, peritoneal lavage; CPE, crude peanut extract; CT, cholera toxin; LN, lymph node; BAL, bronchoalveolar lavage; GI, gastrointestinal; i.d., intradermal; i.n., intranasal; DIG, digoxigenin; DC, dendritic cell.
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