Longitudinal Egg-Specific Regulatory T- and B-Cell Development: Insights From Primary Prevention Clinical Trials Examining the Timing of Egg Introduction

Abstract

During early egg introduction to infants, regulatory immune cells involved in tolerance development were studied.In the study, the researchers included 124 Australian infants from 2 randomized controlled trials of early introduction of egg for the primary prevention of egg allergy.Two separate early introduction egg study cohorts (BEAT and STEP) were managed for 12 months. Cryopreserved peripheral blood mononuclear cells were ovalbumin-stimulated in vitro. Ovalbumin-specific regulatory T cells were then identified by flow cytometry detection of forkhead box P3 and interleukin 10 (IL-10). Ovalbumin-specific B regulatory cells were detected by coexpression of fluorescence-conjugated ovalbumin and IL-10.There were decreased ovalbumin-specific regulatory B cells and impaired ovalbumin-specific regulatory T cells in egg-allergic infants, compared with egg-tolerant infants. Ovalbumin-specific age-dependent regulatory T-cell expansion was also decreased in non–egg-allergic infants who did not introduce egg early.Ovalbumin-specific B and T cells were correlated with clinical egg tolerance. The timing of egg introduction also correlated with ovalbumin-specific T regulatory cell expansion. This study reveals the importance of the adaptive immune system in food tolerance. Future studies in which researchers evaluate the role and ratio of Th2 to T regulatory ovalbumin-specific cells would be helpful.Egg allergy is one of the most common pediatric food allergies in the United States and the world. The US-published 2017 Addendum Guidelines for the Prevention of Peanut Allergy has not formally addressed early egg introduction. Early egg introduction has been associated with a decreased risk of egg allergy. With this study, the researchers support the protective effects of early egg introduction and the underlying immunologic pathophysiology.