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Clin Exp Allergy. 2018 Jul;48(7):825-836. doi: 10.1111/cea.13161. Epub 2018 May 29.

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

Author information

1
Division of Immunology, Boston Children's Hospital and the Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
2
Division of Immunology, Section of Pediatrics, Department of Health Sciences, University of Florence and Anna Meyer Children's Hospital, Florence, Italy.
3
Genentech, South San Francisco, CA, USA.

Abstract

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.

KEYWORDS:

FOXP3; food allergy; omalizumab; oral immunotherapy; regulatory T cells

PMID:
29700872
PMCID:
PMC6021220
[Available on 2019-07-01]
DOI:
10.1111/cea.13161

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