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Clinical and Developmental Immunology
Volume 2012, Article ID 623474, 8 pages
Review Article

Induction of Tolerance via the Sublingual Route: Mechanisms and Applications

Département Scientifique, Stallergènes SA, 6 rue Alexis de Tocqueville, 92160 Antony, France

Received 30 May 2011; Accepted 23 September 2011

Academic Editor: Donna-Marie McCafferty

Copyright © 2012 Philippe Moingeon and Laurent Mascarell. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The clinical efficacy of sublingual immunotherapy (SLIT) with natural allergen extracts has been established in IgE-dependent respiratory allergies to grass or tree pollens, as well as house dust mites. Sublingual vaccines have an excellent safety record, documented with approximately 2 billion doses administered, as of today, in humans. The oral immune system comprises various antigen-presenting cells, including Langerhans cells, as well as myeloid and plasmacytoid dendritic cells (DCs) with a distinct localisation in the mucosa, along the lamina propria and in subepithelial tissues, respectively. In the absence of danger signals, all these DC subsets are tolerogenic in that they support the differentiation of Th1- and IL10-producing regulatory CD4+ T cells. Oral tissues contain limited numbers of mast cells and eosinophils, mostly located in submucosal areas, thereby explaining the good safety profile of SLIT. Resident oral Th1, Th2, and Th17 CD4+ T cells are located along the lamina propria, likely representing a defence mechanism against infectious pathogens. Second-generation sublingual vaccines are being developed, based upon recombinant allergens expressed in a native conformation, possibly formulated with Th1/T reg adjuvants and/or mucoadhesive particulate vector systems specifically designed to target oral dendritic cells.