Update on Immune Mechanisms Associated with Sublingual Immunotherapy: Practical Implications for the Clinician

Sublingual immunotherapy (SLIT) is established as a safe and efficacious treatment for patients with type I respiratory allergies. The ability of SLIT to elicit antigen (allergen)-specific tolerance is linked to the peculiar biology of oral antigen-presenting cells. In the absence of danger signals, Langerhans cells, myeloid dendritic cells, and macrophages located in oral tissues, tonsils, and draining cervical lymph nodes are biased toward the induction of TH1 and IL-10-producing CD4+ regulatory T cells, thus supporting tolerance as opposed to inflammation. Sublingual administration does not lead to any detectable systemic exposure of intact allergens nor to IgE neosensitization. Oral tissues contain limited numbers of mast cells located in submucosal areas, thereby explaining the well-established safety profile of SLIT, with mostly local but rare systemic reactions. The induction of CD4+ regulatory T cells and blocking anti-inflammatory IgGs or IgAs are considered important for tolerance induction after SLIT. Specific molecular signatures associated with tolerogenic dendritic cells were recently reported during the onset of SLIT efficacy in the peripheral blood of patients exhibiting clinical benefit. Collectively, these observations confirm the induction of strong allergen-specific suppressive/tolerogenic immune responses during SLIT and pave the ground for the identification of biomarkers of efficacy. Practical implications of this emerging scientific knowledge are presented (1) to support the rational design of second-generation sublingual vaccines based on purified allergens, vector systems and/or adjuvants and (2) to help the clinician in decision making during his/her practice.