Mechanisms of allergen-specific immunotherapy: Multiple suppressor factors at work in immune tolerance to allergens

Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a desensitizing therapy for IgE-mediated allergic diseases and represents a potentially curative way of treatment. The mechanisms of action of AIT include the induction of very early desensitization of mast cells and baso...

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Bibliographic Details
Published in:	Journal of allergy and clinical immunology Vol. 133; no. 3; pp. 621 - 631
Main Authors:	Akdis, Mübeccel, Akdis, Cezmi A.
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01.03.2014 Elsevier Elsevier Limited
Subjects:	allergen immunotherapy Allergens - immunology Allergies Allergy and Immunology Animals Asthma B cells B-Lymphocytes, Regulatory - immunology basophils Basophils - physiology Biological and medical sciences Biopsy Cytokines Desensitization, Immunologic Disease eosinophils Food allergies Forkhead Transcription Factors - physiology Fundamental and applied biological sciences. Psychology Fundamental immunology Humans IgE IgG IL-10 Immune system Immune Tolerance Immunopathology Immunotherapy Interleukin-10 - physiology Ligands Lymphocytes mast cells Mast Cells - physiology Medical sciences Psoriasis Receptors, Histamine H2 - physiology Regulatory T cells Rodents Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis T cells T helper cells T-Lymphocytes, Regulatory - immunology TGF-β Transcription factors Transforming Growth Factor beta - physiology VIT PLA IgE IgG eosinophils HR basophils Regulatory T cells T cells mast cells SHP-1 Breg LPR immune tolerance immunotherapy TGF-β CTLA-4 TLR ICOS BR1 SLIT allergen immunotherapy Treg B cells AIT FOXP3 IL-10 pDC TR1 T helper cells PD-1 DC Src homology domain 2–containing protein tyrosine phosphatase 1 Programmed death 1 Forkhead box protein 3 Regulatory T IL-10–secreting regulatory B Histamine receptor Toll-like receptor Dendritic cell B R1 Inducible costimulator IL-10–secreting regulatory T Regulatory B Phospholipase A 2 T R1 Plasmacytoid dendritic cell Cytotoxic T lymphocyte antigen 4 Late-phase response Venom immunotherapy Sublingual immunotherapy Allergen-specific immunotherapy Allergy Transforming growth factor β Granulocyte Helper cell Basophil Mechanism Immunology Immunotherapy T-Lymphocyte Suppressor Regulatory cell Immunopathology Immunoglobulins Desensitization Multiple Cytokine B-Lymphocyte Eosinophil Treatment Immune tolerance Interleukin 10 Mast cell Allergen
ISSN:	0091-6749, 1097-6825, 1097-6825
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Summary:	Allergen-specific immunotherapy (AIT) has been used for more than 100 years as a desensitizing therapy for IgE-mediated allergic diseases and represents a potentially curative way of treatment. The mechanisms of action of AIT include the induction of very early desensitization of mast cells and basophils; generation of regulatory T and regulatory B (Breg) cell responses; regulation of IgE and IgG4; decreases in numbers and activity of eosinophils and mast cells in mucosal allergic tissues; and decreases in the activity of basophils in circulation. Skewing of allergen-specific effector T and effector B cells to a regulatory phenotype appears as a key event in the course of AIT and normal immune response to allergens. Recently, inducible IL-10–secreting Breg cells were also demonstrated to contribute to allergen tolerance through suppression of effector T cells and selective induction of IgG4 isotype antibodies. Allergen-specific regulatory T and Breg cells orchestrate a general immunoregulatory activity, which can be summarized as suppression of cytokines from inflammatory dendritic cells; suppression of effector TH1, TH2, and TH17 cells; suppression of allergen-specific IgE and induction of IgG4; and suppression of migration of mast cells, basophils, eosinophils, and effector T cells to tissues. A detailed knowledge of the mechanisms of AIT is not only important in designing the prevention and treatment of allergic diseases but might also find applications in the treatment of autoimmune diseases, organ transplantation, chronic infection, and cancer.
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ISSN:	0091-6749 1097-6825 1097-6825
DOI:	10.1016/j.jaci.2013.12.1088