title: Longitudinal relationship of early life immunomodulatory T cell phenotype and function to development of allergic sensitization in an urban cohort.
abstract: BACKGROUND
  Immunomodulatory T cells are thought to influence development of allergy and asthma, but early life longitudinal data on their phenotype and function are lacking.
  
  
  OBJECTIVE
  As part of the Urban Environment and Childhood Asthma (URECA) study, we investigated the development of immunomodulatory T cell phenotype and function, and characterized their relation to allergic disease progression from birth through to 2 years of age.
  
  
  METHODS
  Immunomodulatory T cell phenotype and function in cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC) at 1 and 2 years of age were characterized by analysing CD25(bright) and FoxP3(+) expression, proliferative responses and cytokine production. The relation of immunomodulatory T cell characteristics to allergic sensitization and disease at 1- and 2-years of age was investigated.
  
  
  RESULTS
  The proportion of CD4(+)CD25(bright) and CD4(+)CD25(+)FoxP3(+)T cells (n = 114, 83, 82 at birth, 1- and 2-years respectively) increased significantly, whereas there were no significant changes in the suppressive function of CD25(+)T cells (n = 78, 71, 81 at birth, 1- and 2-years respectively). Birth immunomodulatory T cell characteristics were not related to subsequent allergic sensitization or disease. However, increases in the numbers of CD4(+)CD25(bright) cells and their ability to suppress lymphoproliferative responses at 1 year of age were associated with reduced allergic sensitization at 1 (P = 0.03) and 2 (P = 0.02) years of age. Production of the anti-inflammatory cytokine IL-10 by CD25(+)T cells appeared to mediate this protective suppressive function. In contrast, by 2 years of age, we observed the emergence of a positive association of CD4(+)CD25(+) FoxP3(+) T cell numbers with allergic sensitization (P = 0.05) and eczema (P = 0.02).
  
  
  CONCLUSIONS
  These findings suggest that the relationship between immunomodulatory T cell subsets, allergic sensitization and eczema is developmentally regulated. In the first year of life, CD4(+)CD25(+) IL-10 producing T cells are associated with a reduced incidence of allergic sensitization. Once allergic sensitization or eczema is established, CD4(+)CD25(+)FoxP3(+)T-reg cells expand to potentially counteract the allergic inflammatory response. Understanding the relationship between development of immunoregulatory T cells and early onset atopy could lead to new preventive strategies for allergic diseases.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. rachel.mcloughlin@tcd.ie
authors.forename: R M
authors.initials: RM
authors.lastname: McLoughlin
authors.forename: A
authors.initials: A
authors.lastname: Calatroni
authors.forename: C M
authors.initials: CM
authors.lastname: Visness
authors.forename: P K
authors.initials: PK
authors.lastname: Wallace
authors.forename: W W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: M
authors.initials: M
authors.lastname: Tuzova
authors.forename: N P
authors.initials: NP
authors.lastname: Ly
authors.forename: B
authors.initials: B
authors.lastname: Ruiz-Perez
authors.forename: M
authors.initials: M
authors.lastname: Kattan
authors.forename: G R
authors.initials: GR
authors.lastname: Bloomberg
authors.forename: H
authors.initials: H
authors.lastname: Lederman
authors.forename: J E
authors.initials: JE
authors.lastname: Gern
authors.forename: D R
authors.initials: DR
authors.lastname: Gold
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014505:Urban Population
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit
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