Immunological mechanisms of allergen-specific immunotherapy

Key PointsAllergen-specific immunotherapy (SIT) for allergic diseases is the oldest form of antigen-specific disease-modifying therapy.Administration of allergen by injection or mucosal (sublingual) application leads to amelioration of clinical symptoms and has lasting effects that exceed the period of treatment.Immunological changes that are associated with SIT include the induction of allergen-specific antibodies (mainly IgG but also IgA) that block the interaction of allergen with IgE, preventing the activation of mast cells and basophils and reducing the IgE-dependent uptake of allergen by antigen-presenting cells (APCs).SIT induces anergy in T cells, induces functional allergen-specific regulatory T-cell populations, and is associated with increased production of interleukin-10 (as well as transforming growth factor-β in some studies) by T cells and APCs.Novel approaches towards SIT include the use of adjuvants to antagonize T-helper-2-cell responses and the use of modified allergen preparations, including recombinant allergens, genetically engineered hypoallergenic allergens, peptides corresponding to T-cell or B-cell epitopes, and allergen fusionproteins.Improved understanding of the mechanisms that are involved in successful SIT will inform the development of novel treatments for other chronic diseases, such as autoimmune and transplantation-related conditions.