- Sciences & innovation
- Desensitisation
- Mechanism
During allergen-specific immunotherapy (SIT), the allergen is captured locally (i.e. at the level of oral mucosa in sublingual route, or site of injection for subcutaneous route) by dendritic cells, which subsequently migrate to proximal lymph nodes, and stimulate T lymphocytes. A central paradigm in SIT has been to reorient allergen-specific T cell responses in atopic patients from Th2 to Th1 or Th0.
Now, there is a growing interest in stimulating a new subset of CD4+ T cells, called regulatory T cells, which are able to down regulate both Th1 and Th2 responses through the production of IL-10 or TGF-ß. During SIT, changes in cytokine production modulate immunoglobulin isotype switch, decreasing IgE production and facilitating IgG4 and IgA responses.
Allergen dosage appears to be critical in influencing T lymphocyte polarisation. This makes high-dose sublingual immunotherapy of particular interest as a method of inducing tolerance against environmental allergens because there are large numbers of Langerhans-like dendritic cells in the oral mucosa that are specialised in allergen capture. Furthermore, the oral mucosa contains only limited numbers of pro-inflammatory cells (such as mast cells), which helps to explain why SLIT has a well-established safety profile.
Specific mechanism of the sublingual route of administration
When exposing individuals to an allergen, sublingual immunotherapy takes advantage of oral tolerance. The evolution and preservation of this important physiological feature ensures that there is immune tolerance to various antigenic stimuli in the environment.
In the oral mucosa, the immune system is geared to induce tolerance to allergens. It has the following characteristics :
- There are large numbers of Langerhans-like dendritic cells, which are highly adapted for allergen uptake by pinocytosis and receptor-mediated mechanisms that allow allergen endocytosis and subsequent presentation to T lymphocytes.[2]
- Preliminary evidence suggests that the oral mucosa contains very few mast cells, a limited number of B cells and no eosinophils
- Antibody responses induced by oral immunisation are predominantly based on IgA rather than IgE.
