Cellular and Humoral Mechanisms of Immune Tolerance in Immediate-Type Allergy Induced by Specific Immunotherapy

The management of immediate-type allergy (ITA) is based on allergen avoidance, symptomatic pharmacological therapy and specific immunotherapy (SIT). Among these, SIT presents the only curative treatment. The efficacy of SIT in the treatment of IgE-mediated ITA has been proven in numerous clinical studies and is well established. This review discusses the relevance of immunoregulative humoral and cellular mechanisms leading to immune tolerance in ITA. Special focus is placed on the role of antibodies potentially interfering with the IgE-mediated immune reaction and regulatory T (T reg ) cells including their immunosuppressive cytokines, which play a critical role in shifting the T helper 2 cell-driven allergic immune response towards allergen tolerance. Distinct subsets of constitutive and inducible T reg cells have been identified inhibiting the activation of allergen-specific effector T cells via cell contact- or cytokine-dependent suppression. Current research suggests that both inducible interleukin-10-producing CD4+ T reg cells and naturally occurring CD4+CD25+ T reg cells actively control allergic responses and that the disturbance of their function or number may contribute to the development or progression of allergy. Thus, the fine balance between allergen-specific T helper 2 and T reg cells constitutes a critical factor for the successful treatment of ITA by SIT.