title: Impact of CD40 ligand, B cells, and mast cells in peanut-induced anaphylactic responses.
abstract: The effector immune mechanisms underlying peanut-induced anaphylaxis remain to be fully elucidated. We investigated the relative contribution of Igs, mast cells (MCs), and FcepsilonRI 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 approximately 8 degrees 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 (Kit(W)/Kit(W-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, FcepsilonRI-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 FcepsilonRI 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.
authors.affiliation: Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Katherine
authors.initials: K
authors.lastname: Arias
authors.forename: David
authors.initials: D
authors.lastname: Alvarez
authors.forename: Ramzi
authors.initials: R
authors.lastname: Fattouh
authors.forename: Tina
authors.initials: T
authors.lastname: Walker
authors.forename: Susanna
authors.initials: S
authors.lastname: Goncharova
authors.forename: Bobae
authors.initials: B
authors.lastname: Kim
authors.forename: Susan
authors.initials: S
authors.lastname: Waserman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Reed
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
mesh_terms: D000707:Anaphylaxis / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006632:Histamine / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D015289:Leukotrienes / Q000097:blood; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D021183:Peanut Hypersensitivity / Q000097:blood / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D016207:Cytokines; D015289:Leukotrienes; D017455:Receptors, IgE; D023201:CD40 Ligand; D007073:Immunoglobulin E; D006632:Histamine