T regulatory cells in allergy: Novel concepts in the pathogenesis, prevention, and treatment of allergic diseases

The identification of T regulatory (TReg) cells as key regulators of immunologic processes in peripheral tolerance to allergens has opened an important era in the prevention and treatment of allergic diseases. Both naturally occurring CD4+CD25+ TReg cells and inducible populations of allergen-specific IL-10-secreting TR1 cells inhibit allergen-specific effector cells in experimental models. Allergen-specific TReg cell responses contribute to the control of allergic inflammation in several ways. Skewing of allergen-specific effector T cells to a TReg phenotype appears to be a crucial event in the development of a healthy immune response to allergens and successful outcome in allergen-specific immunotherapy. The increased levels of IL-10 and TGF-β produced by TReg cells can potently suppress IgE production while simultaneously increasing the production of the noninflammatory antibody isotypes IgG4 and IgA, respectively. TReg cells directly or indirectly suppress effector cells of allergic inflammation, such as mast cells, basophils, and eosinophils, and contribute to remodeling in asthma and atopic dermatitis. In addition, mediators of allergic inflammation that trigger cyclic AMP-associated G protein-coupled receptors, such as histamine receptor 2, might play a role in peripheral tolerance mechanisms against allergens. Current strategies for drug development and allergen-specific immunotherapy exploit these observations with the potential to provide cure for allergic diseases.