title: Mechanisms of immune tolerance to allergens.
abstract: In allergic diseases, immune responses are induced by normally well-tolerated allergens, which result in chronic inflammation characterized by antibody secretion and T cell activation. For almost 100 years, allergen-specific immunotherapy (allergen-SIT) has been the potentially curative and antigen-specific method for the treatment of allergic diseases. Allergen-SIT alters the course of allergic diseases and can reduce allergic symptoms and medication use. The key mechanism behind allergen-SIT is the induction of peripheral T cell tolerance by altering the balance between Th cells and regulatory T cells. Both naturally occurring thymus-derived FOXP3(+)CD4(+)CD25(+) regulatory T cells and inducible type 1 regulatory T cells suppress the development of allergic diseases via several mechanisms including suppression of dendritic cells, Th cells, mast cells, eosinophils and basophils; suppression of inflammatory cell migration to tissues; and decrease of the ratio between allergen-specific IgE and IgG4 antibodies. These effects are mainly mediated by the suppressive cytokines IL-10 and TGF-β. Knowledge of this molecular basis is crucial to understanding the regulation of the immune response and their possible therapeutic applications for allergic diseases.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujita
authors.forename: Norbert
authors.initials: N
authors.lastname: Meyer
authors.forename: Mübeccel
authors.initials: M
authors.lastname: Akdis
authors.forename: Cezmi A
authors.initials: CA
authors.lastname: Akdis
mesh_terms: D000485:Allergens / Q000276:immunology*; D003888:Desensitization, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000378:metabolism; D007074:Immunoglobulin G / Q000502:physiology; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007073:Immunoglobulin E