Immunoglobulin (Ig) E–mediated food allergy is a type 2 helper T cell (TH2)–dependent disease whose prevalence is increasing in industrialized countries as a direct consequence of reduced tolerance to food antigens. The generation of regulatory T cells (Treg) is a key component of oral tolerance, and compelling experimental evidence has demonstrated that functional allergen-specific Treg cells play a major role in healthy immune responses to allergens and clinically successful allergen-specific immunotherapy. In the particular case of IgE-mediated food allergy, further investigations are required to firmly demonstrate the role of Treg cells during desensitization, induction of tolerance, or both, and several studies have also suggested a key role for these cells in healthy responses to food allergens. Treg cells are able to suppress the sensitization and effector phases of allergic reactions via several mechanisms of action based on multiple soluble and surface-binding molecules. Our knowledge of the mechanisms governing the generation of food allergen–specific Treg cells in the gastrointestinal mucosa, including the specific dendritic cell subsets involved in such processes, has increased significantly over the last decade. The identification of alternative tissues where oral tolerance to food allergens might occur in vivo is crucial, not only for a better understanding of the pathophysiology of food allergy, but also for the development of alternative therapeutic interventions. Recent findings demonstrate that oral tolerance can be induced in the tonsils through generation and maintenance of functional allergen-specific Treg cells. Further investigation in this area could pave the way for novel treatments of food allergy and other immune tolerance–related diseases.

Key words: Allergy. IgE-mediated food allergy. Allergen-specific immunotherapy. Tolerance. Desensitization. Regulatory T cells. Dendritic cells.