title: High proportions of FOXP3(+) CD25(high) T cells in neonates are positively associated with allergic sensitization later in childhood.
abstract: BACKGROUND
  The role of FOXP3(+) regulatory T cells in the prevention against sensitization and allergy development is controversial.
  
  
  OBJECTIVE
  We followed 65 newborn Swedish children from farming and non-farming families from birth to 3 years of age and investigated the relation between CD4(+) T cell subsets in blood samples and development of sensitization and allergic disease.
  
  
  METHODS
  The proportions of FOXP3(+) CD25(high) , CTLA-4(+) CD25(+) , CD45RO(+) , HLA-DR(+) , CCR4(+) or α4β7(+) within the CD4(+) T cell population were examined by flow cytometry of blood samples at several time-points. Mononuclear cells were isolated from blood and stimulated with birch allergen, ovalbumin or the mitogen PHA, and the levels of IL-1β, IL-6, TNF, IFN-γ, IL-5 and IL-13 were measured. A clinical evaluation regarding the presence of allergen-specific IgE and allergy was performed at 18 and 36 months of age.
  
  
  RESULTS
  Multivariate discriminant analysis revealed that children who were sensitized at 18 or 36 months of age had higher proportions of FOXP3(+) CD25(high) T cells at birth and at 3 days of life than children who remained non-sensitized, whereas allergy was unrelated to the neonatal proportions of these cells. The proportions of CTLA-4(+) CD25(+) T cells were unrelated to both sensitization and allergy. The association between higher proportions of FOXP3(+) CD25(high) T cells and sensitization persisted after exclusion of farmer's children. Finally, a farming environment was associated with lower proportions of FOXP3(+) CD25(high) T cells in early infancy and to a more prominent T cell memory conversion and cytokine production.
  
  
  CONCLUSIONS
  Our results indicate that high proportions of FOXP3(+) CD25(high) T cells in neonates are not protective against later sensitization or development of allergy.
authors: Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors: A
authors: A
authors: Strömbeck
authors: H
authors: H
authors: Rabe
authors: A-C
authors: AC
authors: Lundell
authors: K
authors: K
authors: Andersson
authors: S
authors: S
authors: Johansen
authors: I
authors: I
authors: Adlerberth
authors: A E
authors: AE
authors: Wold
authors: B
authors: B
authors: Hesselmar
authors: A
authors: A
authors: Rudin
mesh_terms: D000367:Age Factors; D000954:Antigens, Surface / Q000378:metabolism; D017756:Aquaculture; D002675:Child, Preschool; D004198:Disease Susceptibility / Q000276:immunology*; D004777:Environment; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D018655:Lymphocyte Count; D012307:Risk Factors; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D007073:Immunoglobulin E
keywords: FOXP3+CD25high T cells; T cell development; allergic sensitization; children; farm; neonates