Update on Immune Mechanisms Associated with Sublingual Immunotherapy: Practical Implications for the Clinician Philippe Moingeon, PhD The Journal of.

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Presentation transcript:

Update on Immune Mechanisms Associated with Sublingual Immunotherapy: Practical Implications for the Clinician Philippe Moingeon, PhD The Journal of Allergy and Clinical Immunology: In Practice Volume 1, Issue 3, Pages 228-241 (May 2013) DOI: 10.1016/j.jaip.2013.03.013 Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 1 Allergen-specific tolerance induction via the sublingual route. The allergen(s) is (are) captured and processed by oral APCs (LCs, MDCs; macrophages) within 15 to 30 minutes. Those APCs loaded with allergen-derived peptides reach cervical lymph nodes within 12 to 24 hours, where they interact with naive CD4+ T cells to induce TH1 and Treg cells with suppressive activity within 2 to 5 days. These CD4+ T cells subsequently migrate into the blood and to tissues, resulting in long-term allergen-specific tolerance. The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 228-241DOI: (10.1016/j.jaip.2013.03.013) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 2 Lack of systemic allergen exposure after sublingual administration. Mice received a ragweed pollen extract either intravenously (IV), subcutaneously (SC), or sublingually (SL). The 40 to 45-kDa Amb a 1 allergen was detected in the serum after 1, 5, 10, 20, 60 minutes with the use of a specific polyclonal rabbit antiserum. Sera from naive animals were used as controls (C). This experiment and others performed in dogs with the use of recombinant Bet v 1 confirmed the absence of detectable systemic exposure of proteins/allergens administered sublingually. The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 228-241DOI: (10.1016/j.jaip.2013.03.013) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Figure 3 Immune changes induced during SLIT. Immune changes include (1) the polarization of allergen-specific CD4+ T-cell responses, with a switch from TH2 to TH1 and Treg-cell profiles, (2) a progressive decrease in specific IgEs and rapid and sustained induction of IgG4s and IgAs, including potential blocking (ie, anti-inflammatory) antibodies, and (3) molecular alterations at the level of innate cells, including basophils and monocytes/monocyte-derived DCs. Immune mechanisms associated with SLIT and SCIT are thought to be similar, with a critical role of the induction of TH1 (immunodeviation) and Treg-cell responses (immunosuppression). The Journal of Allergy and Clinical Immunology: In Practice 2013 1, 228-241DOI: (10.1016/j.jaip.2013.03.013) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions