Chapter 4. Mechanisms of allergen immunotherapy

The molecular and cellular mechanisms of allergen-specific immunotherapy (SIT) have recently been investigated. It appears that, similar to a normal immune response to allergen, the generation of allergen-specific, regulatory/suppressor T cells plays a key role in succcessful SIT. T cells before and after SIT and exposure to high allergen doses, showed distinct cytokine profiles. The frequency of interleukin (IL)-10-producing T cells revealed that allergen-specific regulatory/suppressor T cells represent a dominant allergen-specific T cell subset in healthy individuals and succesful SIT. IL-10 and transforming growth factor (TGF)-β induce tolerance in T cells and regulate the specific immunity. Our results demonstrate that IL-10 and transforming growth factor (TGF)-β secreting regulatory/suppressor T cells control the healthy allergen response in cooperation with other suppressor molecules, and depletion of this T cell subset or blocking of expressed suppressor molecules, enhanced the specific response. Furthermore, IL-10 is able to generate noninflammatory IgG₄ antibodies and TGF-β is a switch and promoting factor for IgA. Both cytokines suppress IgE formation. Thus, induction of specific unresponsiveness (tolerance) and development of allergen-specific regulatory CD4⁺, CD25⁺ T cells secreting IL-10 and/or TGF-β and the recovery of effector T cells by cytokines from the tissue microenvironment, represent key steps in SIT of allergy and natural immunity to allergens.