Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions - 31/10/12
, Anita H.J. van den Biggelaar, PhD a, ⁎, , ‡ 
Corresponding author: Anita H. J. van den Biggelaar, PhD, Crucell, Innovation & Discovery Lab, Archimedesweg 4-6, 2333 CN, The Netherlands.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.
Le texte complet de cet article est disponible en PDF.Key words : Antigen-presenting cell, cord blood, hygiene hypothesis, neonatal, T cell, Papua New Guinea, Australia
Abbreviations used : APC, CBMC, DC, ILT, mDC, pDC, PI, PNG
Plan
| Supported by an Australian National Health and Medical Research Council (NHMRC) Project Grant (513836) and a University of Western Australia Research Grants Scheme. J.G.L. received an Australian Postgraduate Award, a Stan and Jean Perron Award, and a Perron Performance Award, and A.H.J.B. was supported by a NHRMC R Douglas Wright Biomedical Career Development Grant (458780). |
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| Disclosure of potential conflict of interest: S. L. Prescott is a Board member for the Nestlé Nutrition Institute (Australasia) and for Danone and has received speakers’ fees from ALK-Abelló. P. C. Richmond has received support for research from the Wellcome Trust and the National Health and Medical Research Council of Australia. W. Pomat has received support for research from the Telethon Institute for Child Health Research and the University of Western Australia. P. M. Siba has received support for research from the Telethon Institute for Child Health Research. A. van den Biggelaar has received support for research from the National Health and Medical Research Council of Australia. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 130 - N° 5
P. 1167 - novembre 2012 Retour au numéro
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