The precise mechanisms underlying the effects of Specific Immunotherapy are not well understood but several studies have shown that Specific Immunotherapy T inhibits both early and late immune responses to allergen exposure.
Recently, there have been many studies aimed at elucidating the mechanisms by which allergen-specific immunotherapy works. Indeed, there are very impressive data defining the immunologic changes and long-lasting immunotolerogenic effects of immunotherapy. Allergen immunotherapy is the only antigen-specific immunomodulatory treatment routinely available. It has been shown to provide long-lasting benefits and to modify the natural history of allergic diseases, preventing the development of neosensitization and asthma in children.
It has long been known that immunotherapy blunts seasonal increases in IgE levels and results in increases in allergen-specific IgG levels (i.e. blocking antibodies), especially of the IgG4 subclass. This results in decreased IgE-mediated histamine release and inhibition of IgE-mediated antigen presentation to T cells. Recent studies have also demonstrated the importance of examining the affinity and specificity of IgG subsequent to immunotherapy. The binding capacity of IgG4 increased, whereas that for IgE decreased after long-term immunotherapy. However, there is a weak correlation between IgG concentration and clinical response to treatment.
In addition to the effects of immunotherapy on immunoglobulins, its effects on lymphocytes have been intensely studied. Some peripheral blood studies have indicated a shift in the balance of T-lymphocyte subsets away from the helper T cell type 2 (Th2) phenotype and toward a Th1 phenotype on the basis of preferential production of interferon ? (IFNy) and decreased production of interleukin-4 (IL-4) and IL-5. However, these findings are not consistent. What is consistent is the demonstration of increased allergen-specific IL-10 during the early stages of immunotherapy. IL-10 has also been shown to be increased in the respiratory mucosa and is produced by a number of cells, including Th1 cells, Th2 cells, regulatory T cells, monocytes–macrophages, dendritic cells, mast cells and eosinophils. IL-10 has a number of biologic consequences that could be important in mediating the immunotolerogenic effects of immunotherapy. These effects include modulation of IL4-induced B-cell IgE production in favor of IgG4, inhibition of IgE-dependent mast cell activation, inhibition of human eosinophil cytokine production and survival, suppression of IL-5, and induction of antigen-specific anergy.
The importance of IL-10, regulatory T cells (Tr cells) and dendritic cells cannot be overemphasized. These cells appear to be critical in the therapeutic effects of immunotherapy and further research to define their role exactly will likely be a fruitful area.
Studies in patients with seasonal allergic rhinitis have shown that SIT attenuates the seasonal influx of eosinophils, basophils and T cells in the nasal mucosa. There is now little doubt that there is Th2 predominance in allergic diseases and SIT has been shown to modulate the Th2/Th1 balance. SIT induces a Th1 response as evidenced by an increase in IFNy production within nasal mucosa. Similar response is seen in patients undergoing venom immunotherapy where there is a reduction in IL-4 production and an increase in IFN? production by peripheral blood lymphocytes.
Recent studies have focused attention on Tr cells that are identified by their CD4+CD25+ phenotype. It has been shown that Tr cells are induced by SIT, leading to IL-10 and transforming growth factor ß (TGFß) production that may have a number of anti-allergic effects including modulation of IL-4-induced B-cell IgE production in favor of IgG4, inhibition of IgE-dependent mast cell activation and inhibition of human eosinophil cytokine production and survival. IL-10 also suppresses production of ‘proallergic’ cytokines, such as IL-5, and is able to induce a state of T-cell unresponsiveness or ‘anergy’ that might occur as a result of IL-10 receptor-dependent blockade of the B7/CD28 co- stimulatory pathway.
