Article

Mechanisms of allergen-specific immunotherapy

Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 01/2011; 127(1):18-27; quiz 28-9. DOI: 10.1016/j.jaci.2010.11.030
Source: PubMed

ABSTRACT Allergen-specific immunotherapy has been used for 100 years as a desensitizing therapy for allergic diseases and represents the potentially curative and specific method of treatment. The mechanisms of action of allergen-specific immunotherapy include the very early desensitization effects, modulation of T-and B-cell responses and related antibody isotypes, and migration of eosinophils, basophils, and mast cells to tissues, as well as release of their mediators. Regulatory T (Treg) cells have been identified as key regulators of immunologic processes in peripheral tolerance to allergens. Skewing of allergen-specific effector T cells to a regulatory phenotype appears as a key event in the development of healthy immune response to allergens and successful outcome in patients undergoing allergen-specific immunotherapy. Naturally occurring forkhead box protein 3-positive CD4(+)CD25(+) Treg cells and inducible T(R)1 cells contribute to the control of allergen-specific immune responses in several major ways, which can be summarized as suppression of dendritic cells that support the generation of effector T cells; suppression of effector T(H)1, T(H)2, and T(H)17 cells; suppression of allergen-specific IgE and induction of IgG4; suppression of mast cells, basophils, and eosinophils; and suppression of effector T-cell migration to tissues. New strategies for immune intervention will likely include targeting of the molecular mechanisms of allergen tolerance and reciprocal regulation of effector and Treg cell subsets.

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Available from: Cezmi A Akdis, Nov 06, 2014
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    • "Studies of T cell activity of allergoids in terms of proliferation of primary T cells, lines or clones, have suggested variable degrees of loss of ability to stimulate T cells, either generally or restricted to some epitopes [12-16]. However, the immunological efficacy of SIT most likely relates to induction of tolerance to allergens through interactions with regulatory T cells (Treg) [17]. Studies with unmodified allergen extracts suggest increased numbers and activity of both CD4+CD25hiFoxp3hi T cells and IL-10 producing T cells after SIT treatment, together with induction of the IL-10-dependent antibody IgG4 [17]. "
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    • "The present study aimed to systemically evaluate the effects of SIT in children. This study was an open clinical observation following the intention-to-treat principle, in which parallel controls and self-controls were established (9). "
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    • "Indeed, induction of Treg cells results in abrogation of food hypersensitivity responses (14, 15). A higher frequency of allergen-specific Treg cells is observed in children that have outgrown cow’s milk allergy and allergen-specific immunotherapy has been shown to induce Treg cells (16, 17), implicating that the induction of Treg cells is essential for mucosal tolerance. "
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