title: Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions.
abstract: BACKGROUND
  One explanation for the high burden of allergic and autoimmune diseases in industrialized countries is inappropriate immune development under modern environmental conditions. There is increasing evidence that the process of immune deviation already begins in utero, but the underlying immunologic mechanisms are not clear.
  
  
  OBJECTIVE
  We sought to identify differences in the function of neonatal antigen-presenting cells (APCs) in children born in settings that are more traditional versus those of modern societies.
  
  
  METHODS
  Cord blood mononuclear cells were collected from newborns from Papua New Guinea (PNG; traditional) and Australia (modern) and compared for differences in APCs and T-cell phenotype and function.
  
  
  RESULTS
  Australian cord naive T cells (CD4(+)CD25(-)CD127(+) cells) showed an enhanced and more rapid proliferative response in an autologous, APC-dependent culture system, a result of differences in neonatal APCs rather than T-cell function. This included an increased capacity to process antigen and to upregulate activation markers after stimulation. In contrast, resting PNG APCs exhibited higher baseline levels of activation and inhibitory markers and were less responsive or nonresponsive to stimulation in vitro.
  
  
  CONCLUSIONS
  This study supports the hypothesis that prenatal environments can influence the developing immune system in utero. Children born under modern environmental conditions exhibit increased APC reactivity at birth compared with children born under traditional environmental conditions. The functionally more quiescent nature of PNG neonatal APCs might protect against the development of harmful inflammatory responses in early life.
authors: Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia.
authors: Joanne G
authors: JG
authors: Lisciandro
authors: Susan L
authors: SL
authors: Prescott
authors: Marie G
authors: MG
authors: Nadal-Sims
authors: Catherine J
authors: CJ
authors: Devitt
authors: Peter C
authors: PC
authors: Richmond
authors: William
authors: W
authors: Pomat
authors: Peter M
authors: PM
authors: Siba
authors: Patrick G
authors: PG
authors: Holt
authors: Deborah H
authors: DH
authors: Strickland
authors: Anita H J
authors: AH
authors: van den Biggelaar
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D001315:Australia; D002478:Cells, Cultured; D002648:Child; D003710:Demography; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007221:Industry; D007231:Infant, Newborn; D008019:Life Style; D008213:Lymphocyte Activation; D010219:Papua New Guinea; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD