Comparison of neonatal T regulatory cell function in Papua New Guinean and Australian newborns

Background:  Environmental changes, including declining microbial exposure, have been linked with the rising incidence of allergic and autoimmune diseases in ‘western’ populations. This potentially occurs by altering early development of immuno-regulatory pathways including T regulatory cells (Treg). There is now increasing evidence that such conditioning begins in utero. Methods:  We compared neonatal Treg from children born under typical western conditions (Australia, AUS) with those of neonates born under more traditional conditions of high microbial burden (Papua New Guinea, PNG). Results:  The frequency of neonatal Treg, defined as CD4+ Foxp3+ CD127− CD25+/high was found to be higher in the cord blood of AUS compared to PNG newborns. However, cord Tregsuppressive function in a small subset of children was qualitatively similar between PNG and AUS newborns in both a Treg depletion assay and a Treg supplementation assay. Conclusions:  These findings do not support the hypothesis that living in a ‘western’ versus more traditional environment leads to poor induction or suppressive function of neonatal Treg. However, environmentally-induced immuno-regulation may potentially occur via alternative mechanisms in PNG newborns that should now be investigated further

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