During the past 20 years, major advances have been made in understanding the molecular and cellular mechanisms of allergen tolerance in humans. The demonstration of T cell tolerance, particularly that mediated by the immune-suppressive functions of IL-10, led to a major conceptual change in this area. Currently, the known essential components of allergen tolerance include the induction of allergen-specific regulatory subsets of T and B cells, the immune-suppressive function of secreted factors, such as IL-10 and TGF-β, the production of IgG4 isotype allergen–specific blocking antibodies, and decreased allergic inflammatory responses by mast cells, basophils, and eosinophils in inflamed tissues.
Cezmi A. Akdis, Mübeccel Akdis
The induction of allergen-specific Tregs, which switch from allergen-specific Th2 cells is one of the initial events in the development of allergen tolerance. The effector cells of allergic inflammation — mast cells, basophils, and eosinophils — are regulated by suppressive and regulatory functions of Tregs in several ways. Treg-secreted IL-10 and TGF-β suppress these cells. Tregs also suppress Th2 cells and their cytokines, preventing the provision of survival factors for these allergy effector cells. IL-10 and TGF-β suppress IgE production by B cells, and meanwhile, IL-10 induces IgG4. IL-10–producing regulatory B cells (Bregs) play a role in suppression of allergen-specific T cells and mainly switch to IgG4-producing plasma cells. H2R plays a role in the suppression of Th2 cells, inflammatory dendritic cells, and basophils.