T-cell responses induced by allergen-specific immunotherapy

Abstract

Allergen-specific immunotherapy is recognized as a highly effective practice in the treatment of patients with severe allergic rhinitis and/or asthma and is recommended by World Health Organization as an integrated part of allergy management strategy. Several studies have shown that allergen-specific immunotherapy, based on the administration of increasing doses of allergen, achieves a hyposensitization and reduces both early and late responses occurring during the natural exposure to the allergen itself. This is the unique antigen-specific immunomodulatory treatment in current use for human diseases. Successful immunotherapy is associated with reductions in symptoms and medication scores and improved quality of life. After interruption it usually confers long-term remission of symptoms and prevents the onset of new sensitizations in children up to a number of years. Subcutaneous immunotherapy usually suppresses the allergen-induced late response in target organs, likely due to the reduction of the infiltration of T cells, eosinophils, basophils, mast cells and neutrophils. In addition to the reduction of cells of allergic inflammation, immunotherapy also decreases inflammatory mediators at the site of allergen exposure. This review provides an update on the immunological T cell responses induced by conventional subcutaneous and sublingual immunotherapy, and gives a unifying view to reconciling the old dualism between immunoredirecting and immunoregulating mechanisms.

Fig. 1

Mechanism of allergen immunotherapy. Allergen immunotherapy induces an altered T cell response which can vary during the course of treatment. IT initially up-regulates few amounts of regulatory and proinflammatory cytokines by antigen-presenting cells (APC) promoting the amplification of both regulatory T cells (T_reg) and T helper type 1 (Th1) cells. The prolonged administration of high doses of allergen, however, induces the local conditions [expression of triggering molecules on APC and the production of high levels of interleukin (IL)-12 and IL-27] favouring the expansion of allergen-specific Th1-like Tr1 cells. These latter cells are recruited into the inflamed tissues and can prime an amplification loop involving the interferon (IFN)-γ-driven activation of APC. This in turn promotes the recruitment and expansion of new Th1-like Tr1 cells, and the increase in microenvironmentral interleukin (IL)-10 and IL-12. IL-12 drives the switch of allergen-specific Th2 and Th17 cells into Th1 and the expansion of natural killer (NK) and NKT cells, all improving the microenvironmental levels of IFN-γ which strengthen APC activation. The consequent excess of IL-10, transforming growth factor-β, IFN-γ and IL-12 can explain most of the immunological alterations shown during allergen immunotherapy.