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      Update in the Mechanisms of Allergen-Specific Immunotheraphy

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          Abstract

          Allergic diseases represent a complex innate and adoptive immune response to natural environmental allergens with Th2-type T cells and allergen-specific IgE predominance. Allergen-specific immunotherapy is the most effective therapeutic approach for disregulated immune response towards allergens by enhancing immune tolerance mechanisms. The main aim of immunotherapy is the generation of allergen nonresponsive or tolerant T cells in sensitized patients and downregulation of predominant T cell- and IgE-mediated immune responses. During allergen-specific immunotherapy, T regulatory cells are generated, which secrete IL-10 and induce allergen-specific B cells for the production of IgG4 antibodies. These mechanisms induce tolerance to antigens that reduces allergic symptoms. Although current knowledge highlights the role of T regulatory cell-mediated immunetolerance, definite mechanisms that lead to a successful clinical outcomes of allergen-specific immunotherapy still remains an open area of research.

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          Most cited references99

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          Plasmacytoid dendritic cells in immunity.

          Human and mouse plasmacytoid dendritic cells have been shown to correspond to a specialized cell population that produces large amounts of type I interferons in response to viruses, the so-called natural interferon-producing cells. As a result, intensive investigation is now focused on the potential functions of plasmacytoid dendritic cells in both innate and adaptive immunity. Here we review recent progress on the characterization of plasmacytoid dendritic cell origin, development, migration and function in immunity and tolerance, as well as their effect on human diseases.
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            Mechanism and regulation of class switch recombination.

            Antibody class switching occurs in mature B cells in response to antigen stimulation and costimulatory signals. It occurs by a unique type of intrachromosomal deletional recombination within special G-rich tandem repeated DNA sequences [called switch, or S, regions located upstream of each of the heavy chain constant (C(H)) region genes, except Cdelta]. The recombination is initiated by the B cell-specific activation-induced cytidine deaminase (AID), which deaminates cytosines in both the donor and acceptor S regions. AID activity converts several dC bases to dU bases in each S region, and the dU bases are then excised by the uracil DNA glycosylase UNG; the resulting abasic sites are nicked by apurinic/apyrimidinic endonuclease (APE). AID attacks both strands of transcriptionally active S regions, but how transcription promotes AID targeting is not entirely clear. Mismatch repair proteins are then involved in converting the resulting single-strand DNA breaks to double-strand breaks with DNA ends appropriate for end-joining recombination. Proteins required for the subsequent S-S recombination include DNA-PK, ATM, Mre11-Rad50-Nbs1, gammaH2AX, 53BP1, Mdc1, and XRCC4-ligase IV. These proteins are important for faithful joining of S regions, and in their absence aberrant recombination and chromosomal translocations involving S regions occur.
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              Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling.

              Th subsets are defined according to their production of lineage-indicating cytokines and functions. In this study, we have identified a subset of human Th cells that infiltrates the epidermis in individuals with inflammatory skin disorders and is characterized by the secretion of IL-22 and TNF-alpha, but not IFN-gamma, IL-4, or IL-17. In analogy to the Th17 subset, cells with this cytokine profile have been named the Th22 subset. Th22 clones derived from patients with psoriasis were stable in culture and exhibited a transcriptome profile clearly separate from those of Th1, Th2, and Th17 cells; it included genes encoding proteins involved in tissue remodeling, such as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. These proinflammatory Th22 responses were synergistically dependent on IL-22 and TNF-alpha. Furthermore, Th22 supernatants enhanced wound healing in an in vitro injury model, which was exclusively dependent on IL-22. In conclusion, the human Th22 subset may represent a separate T cell subset with a distinct identity with respect to gene expression and function, present within the epidermal layer in inflammatory skin diseases. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders.
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                Author and article information

                Journal
                Allergy Asthma Immunol Res
                AAIR
                Allergy, Asthma & Immunology Research
                The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
                2092-7355
                2092-7363
                January 2011
                16 November 2010
                : 3
                : 1
                : 11-20
                Affiliations
                [1 ]Division of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.
                [2 ]Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
                Author notes
                Correspondence to: Cezmi A. Akdis, MD, Swiss Institute of Allergy and Asthma Research (SIAF), 22 Obere Strasse, CH-7270 Davos, Switzerland. Tel: +41-81-410-08-48; Fax: +41-81-410-08-40; akdisac@ 123456siaf.uzh.ch
                Article
                10.4168/aair.2011.3.1.11
                3005313
                21217920
                c91ec971-35ab-474c-b0f4-493c8df4d8d4
                Copyright © 2011 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 June 2010
                : 07 September 2010
                Categories
                Review

                Immunology
                allergen-specific immunotheraphy,dendiritic cells,t regulatory cells,allergy
                Immunology
                allergen-specific immunotheraphy, dendiritic cells, t regulatory cells, allergy

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