title: Mechanisms of allergen-specific immunotherapy and novel ways for vaccine development.
abstract: Allergen-specific immunotherapy (SIT) is the only available curative treatment of allergic diseases. Recent evidence provided a plausible explanation to its multiple mechanisms inducing both rapid desensitization and long-term allergen-specific immune tolerance, and suppression of allergic inflammation in the affected tissues. During SIT, peripheral tolerance is induced by the generation of allergen-specific regulatory T cells, which suppress proliferative and cytokine responses against the allergen of interest. Regulatory T cells are characterized by IL-10 and TGF-beta secretion and expression of important cell surface suppressive molecules such as cytotoxic T lymphocyte antigen-4 and programmed death-1 that directly or indirectly influence effector cells of allergic inflammation, such as mast cells, basophils and eosinophils. Regulatory T cells and particularly IL-10 also have an influence on B cells, suppressing IgE production and inducing the production of blocking type IgG4 antibodies. In addition, development of allergen-specific B regulatory cells that produce IL-10 and develop into IgG4 producing plasma cells represent essential players in peripheral tolerance. These findings together with the new biotechnological approaches create a platform for development of the advanced vaccines. Moreover, reliable biomarkers could be selected and validated with the intention to select the patients who will benefit most from this immune-modifying treatment. Thus, allergen-SIT could provide a complete cure for a larger number of allergic patients and novel preventive approaches need to be elaborated.
authors.affiliation: Department of Clinical Immunology, Wroclaw Medical University, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Jutel
authors.forename: Willem
authors.initials: W
authors.lastname: Van de Veen
authors.forename: Ioana
authors.initials: I
authors.lastname: Agache
authors.forename: Kürsat A
authors.initials: KA
authors.lastname: Azkur
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; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D001491:Basophils / Q000276:immunology; D060908:CTLA-4 Antigen / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods* / Q000639:trends; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
chemical_list: D000485:Allergens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta; D014612:Vaccines; D016753:Interleukin-10; D007073:Immunoglobulin E