Oral immunotherapy with omalizumab reverses the Th2 cell‐like programme of regulatory T cells and restores their function

• Published in: Clinical and experimental allergy Vol. 48; no. 7; pp. 825 - 836
• Main Authors: Abdel‐Gadir, A., Schneider, L., Casini, A., Charbonnier, L.‐M., Little, S. V., Harrington, T., Umetsu, D. T., Rachid, R., Chatila, T. A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2018
• Subjects: Allergens; Cell activation; Cell proliferation; Flow cytometry; Food allergies; food allergy; FOXP3; Helper cells; Immunoglobulin E; Immunoregulation; Immunotherapy; Lymphocytes; Lymphocytes T; Monoclonal antibodies; omalizumab; oral immunotherapy; Peripheral blood; Phenotypes; regulatory T cells; T cell receptors; regulatory T cells; omalizumab; oral immunotherapy; FOXP3; food allergy
• ISSN: 0954-7894; 1365-2222; 1365-2222
• DOI: 10.1111/cea.13161

Summary Background Oral immunotherapy (OIT) successfully desensitizes patients with food allergies, but the immune mechanisms mediating its efficacy remain obscure. Objectives We tested the hypothesis that allergen‐specific regulatory T (Treg) cell function is impaired in food allergy and is restored by anti‐IgE antibody (omalizumab)‐supplemented OIT. Methods Peanut‐specific T effector (Teff) and Treg cell proliferative responses, activation markers and cytokine expression were analysed by flow cytometry in 13 peanut‐allergic subjects before the start of omalizumab‐supplemented OIT and periodically in some subjects thereafter for up to 2 years. Peripheral blood regulatory T cells (Treg cells) were analysed for their peanut‐specific suppressor function before and at 1 year following OIT. This study was registered on ClinicalTrials.gov (NCT01290913). Results Proliferation of allergen‐specific Teff and Treg cells precipitously declined following the initiation of omalizumab therapy prior to OIT, followed by partial recovery after the initiation of OIT. At baseline, peanut‐specific Treg cells exhibited a Th2 cell‐like phenotype, characterized by increased IL‐4 expression, which progressively reversed upon OIT. Peanut‐specific Treg cell suppressor activity was absent at the start of omalizumab/OIT therapy but became robust following OIT. Absent peanut‐specific Treg cell function could also be recovered by the acute blockade of IL‐4/IL‐4R receptor signalling in Treg cells, which inhibited their IL‐4 production. Conclusions and Clinical Relevance OIT supplemented by omalizumab promotes allergen desensitization through an initial omalizumab‐dependent step that acutely depletes allergen‐reactive T cells, followed by an increase in allergen‐specific Treg cell activity due to the reversal of their Th2 cell‐like programme. Improved Treg cell function may be a key mechanism by which OIT ameliorates food allergy.