title: A novel model of sensitization and oral tolerance to peanut protein.
abstract: The prevalence of food allergic diseases is rising and poses an increasing clinical problem. Peanut allergy affects around 1% of the population and is a common food allergy associated with severe clinical manifestations. The exact route of primary sensitization is unknown although the gastrointestinal immune system is likely to play an important role. Exposure of the gastrointestinal tract to soluble antigens normally leads to a state of antigen-specific systemic hyporesponsiveness (oral tolerance). A deviation from this process is thought to be responsible for food-allergic diseases. In this study, we have developed a murine model to investigate immunoregulatory processes after ingestion of peanut protein and compared this to a model of oral tolerance to chicken egg ovalbumin (OVA). We demonstrate that oral tolerance induction is highly dose dependent and differs for the allergenic proteins peanut and OVA. Tolerance to peanut requires a significantly higher oral dose than tolerance to OVA. Low doses of peanut are more likely to induce oral sensitization and increased production of interleukin-4 and specific immunoglobulin E upon challenge. When tolerance is induced both T helper 1 and 2 responses are suppressed. These results show that oral tolerance to peanut can be induced experimentally but that peanut proteins have a potent sensitizing effect. This model can now be used to define regulatory mechanisms following oral exposure to allergenic proteins on local, mucosal and systemic immunity and to investigate the immunomodulating effects of non-oral routes of allergen exposure on the development of allergic sensitization to peanut and other food allergens.
authors.affiliation: Immunobiology Unit, Institute of Child Health, University College London, UK. j.strid@ich.ucl.ac.uk
authors.forename: Jessica
authors.initials: J
authors.lastname: Strid
authors.forename: Melanie
authors.initials: M
authors.lastname: Thomson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hourihane
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.forename: Stephan
authors.initials: S
authors.lastname: Strobel
mesh_terms: D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D010367:Arachis / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004044:Dietary Proteins / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D006968:Hypersensitivity, Delayed; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D021183:Peanut Hypersensitivity / Q000276:immunology*; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D004044:Dietary Proteins; D010940:Plant Proteins; D010047:Ovalbumin; D005620:Freund's Adjuvant