Allergen-specific immunological tolerance

Allergen-specific immunological tolerance refers to the immune system's adapted state of noninflammatory reactivity to specific allergens, preventing type 2 allergic responses characterized by Th2 cells, IgE production, and eosinophil infiltration.[1][2][3] It is primarily induced through allergen-specific immunotherapy (AIT), which promotes regulatory T cell subsets like IL-10-secreting Tr1 cells, FOXP3+ nTregs, and TGF-β-producing Th3 cells, leading to suppression of effector cells such as mast cells, basophils, and eosinophils.[1][5] Key mechanisms include cytokine-mediated inhibition (IL-10 blocks costimulatory signals on T cells and APCs; TGF-β suppresses IgE class-switching), promotion of noninflammatory IgG4 blocking antibodies, and T cell anergy or deletion.[1][2][4] In diseases like asthma, rhinitis, and food allergies, failure of this tolerance underlies chronic inflammation, while its induction via AIT offers the only disease-modifying treatment, reducing symptoms and medication needs long-term.[1][3] Challenges include ensuring antigen-specificity to avoid bystander effects and monitoring for initial hypersensitivity risks during therapy buildup.[4][5]

Other names

Allergen tolerancePeripheral tolerance to allergensAllergen-specific immune tolerance

Mechanism of action involves the induction of allergen-specific regulatory T cells (Tr1 cells, nTregs, iTregs), which promote IL-10 and TGF-β secretion. This leads to the suppression of Th2 cells and effector cells (eosinophils, mast cells, basophils), a shift from IgE to IgG4 antibodies, and T cell anergy and apoptosis.