Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions.

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.