title: Food-allergic infants have impaired regulatory T-cell responses following in vivo allergen exposure.
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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Thanh D
authors.initials: TD
authors.lastname: Dang
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.|Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Vic., Australia.|Institute of Inflammation and Repair, University of Manchester, Manchester, UK.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Allen
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.
authors.forename: David
authors.initials: D
authors.lastname: J Martino
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Koplin
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Licciardi
authors.affiliation: Murdoch Childrens Research Institute, Parkville, Vic., Australia.|Department of Paediatrics, University of Melbourne, Parkville, Vic., Australia.|Department of Allergy and Immunology, Royal Children's Hospital, Parkville, Vic., Australia.
authors.forename: Mimi L K
authors.initials: ML
authors.lastname: Tang
mesh_terms: D000485:Allergens; D010367:Arachis / Q000009:adverse effects / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002478:Cells, Cultured; D004032:Diet / Q000009:adverse effects*; D021181:Egg Hypersensitivity / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D004531:Eggs / Q000009:adverse effects; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007223:Infant; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D009754:Nuts / Q000009:adverse effects / Q000276:immunology; D021183:Peanut Hypersensitivity / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000485:Allergens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit
keywords: FoxP3; HealthNuts; Treg; egg allergy; food allergy; oral food challenge; peanut allergy; regulatory T cells