Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure

Pediatr Allergy Immunol. 2016 Feb;27(1):35-43. doi: 10.1111/pai.12498. Epub 2015 Nov 23.

Abstract

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-sensitized but tolerant, and healthy (non-sensitized 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 sensitization (n = 35), or who were non-sensitized non-allergic (n = 15) were studied. All subjects underwent oral food challenge (OFC) to egg or peanut. PBMCs were obtained within 1 h 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-sensitized 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-sensitized (14.6 ± 1.24) and non-allergic subjects (16.2 ± 1.23).

Conclusion: Our data suggest that the state of allergen sensitization 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 vs. sensitization without allergic reaction.

Keywords: FoxP3; HealthNuts; Treg; egg allergy; food allergy; oral food challenge; peanut allergy; regulatory T cells.

MeSH terms

  • Allergens*
  • Arachis / adverse effects
  • Arachis / immunology
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cells, Cultured
  • Diet / adverse effects*
  • Egg Hypersensitivity / diagnosis
  • Egg Hypersensitivity / immunology*
  • Egg Hypersensitivity / metabolism
  • Eggs / adverse effects
  • Female
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Infant
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation
  • Male
  • Nuts / adverse effects
  • Nuts / immunology
  • Peanut Hypersensitivity / diagnosis
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Time Factors

Substances

  • Allergens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit