Specific Immunotherapy and Central Immune System

Despite the current knowledge, the mechanisms by which the specific immunotherapy (SIT) achieves clinical improvement remains unclear. However, it is now clear that the immune tolerance is one of the major targets of this kind of treatment. Immune tolerance depends on different mechanisms, including T-cell anergy, T-cell depletion by apoptosis, and active immune suppression (Akdis & Akdis, 2011). One of the goals of SIT is the induction of tolerance to allergens to which the patient is sensitized. IL-10 is probably a relevant cytokine induced by this treatment and is associated to regulatory T cells (T-regs) that actively control or suppress the function of other cells, generally in an inhibitory pattern (Frew, 2010). The changes in microenvironment due to the decrease in histamine and PGE2 release by mast cell, and the IL-10 and TGF- release by dendritic cells (DC) could switch the T-cell population into T-regs. These alterations will then lead to tolerance (Schmidt-Weber & Blaser 2005). Much of the knowledge about SIT has been based on studies using subcutaneous route of administration (SCIT), but increasing data is now available based on studies using sublingual immunotherapy (SLIT). The sublingual mucosa, where the deposition of the extract occurs, has very particular characteristics, quite different from the cellular subcutaneous tissue. The dendritic cells present in the buccal region are distinct from the Langerhans cells present in the skin. These cells present, constitutively, receptors with high affinity for IgE, FcRI+, MHC class I and II molecules, as well as co-stimulation molecules, namely CD40, CD80/B7.1 and CD86/B7.2 (Allam et al., 2006). There is also expression of CD14, a lipopolysaccharide (LPS) receptor, which is relevant for the modulation of Th2 and Th1. In SLIT, the allergen is captured by the DC cell by C-lectin endocytosis receptors and/or by ligation to the IgE on the surface. After the internalization, the migration to the regional lymphoid nodules occurs, and it is then presented to the T cells (Geijtenbeek, 2006). A study that compares the DC population in the oral and nasal mucosa was able to demonstrate that only the DC myeloid type is profusely present in the oral region, in contrast with the nasal mucosa where both populations are present (Allam et al., 2006). Another very important difference is the high expression levels of FcRI in the oral mucosa, which is almost absent in the skin’s Langerhans cells (Allam et al., 2003). Furthermore, the expression levels of MHC class I and II molecules, CD40, CD80 and CD86 is significantly higher in oral DC than in the skin.