Mechanisms of allergen-specific immunotherapy

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. (J Allergy Clin Immunol 2011;127:18-27.)