Scientific Study

BACKGROUND: Regulatory T cells (Tregs) are critical for development of oral tolerance, and studies suggest that dysfunction of Tregs may lead to food allergy. However to date no study has investigated Treg responses following in vivo exposure to peanut or egg allergens in humans. OBJECTIVES: To examine changes in peripheral blood CD4+ CD25+ FoxP3+ Treg populations (total, activated, and naive) in food allergic, food-sensitised but tolerant, and healthy (non-sensitised non-allergic) patients over time following in vivo allergen exposure. METHODS: A subset of infants from the HealthNuts study with egg or peanut allergy (n=37), egg or peanut sensitisation (n=35), or who were non-sensitised non-allergic (n=15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMC were obtained within 1 hour of OFC (in vivo allergen exposure); and Treg populations enumerated ex vivo on day 0, and after 2 and 6 days rest in vitro. RESULTS: Non-allergic infants showed stable total Treg frequencies over time; food-sensitised infants had a transient fall in Treg percentage with recovery to baseline by day 6 (6.87% day 0, 5.27% day 2, 6.5% day 6); and food allergic infants showed persistent reduction in Treg (6.85% day 0, 5.4% day 2, 6.2% day 6) following in vivo allergen exposure. Furthermore, food allergic infants had a significantly lower ratio of activated Treg:activated T-cells (10.5±0.77) at day 0 compared to food-sensitised (14.6±1.24) and non-allergic subjects (16.2±1.23). CONCLUSION: Our data suggest that the state of allergen sensitisation is associated with depletion of Treg following allergen exposure. Impaired capacity to regenerate the Treg pool following allergen exposure may be an important factor that determines clinical allergy versus sensitisation without allergic reaction.