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Comparison of neonatal T regulatory cell function in Papua New Guinean and Australian newborns
Joanne G Lisciandro1, Susan L Prescott, Marie G Nadal-Sims
1Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia.
Insights
Neonatal T regulatory cells (T(reg)) were higher in Australian newborns than in those from Papua New Guinea. However, their function was similar, suggesting alternative immune regulation in traditional environments.
Area of Science:
- Immunology
- Environmental Health
- Developmental Biology
Background:
- Declining microbial exposure in Western environments is linked to increased allergies and autoimmune diseases.
- Immuno-regulatory pathways, including T regulatory cells (T(reg)), may be altered by environmental changes starting in utero.
- Early-life immune conditioning is crucial for preventing immune dysregulation.
Purpose of the Study:
- To compare neonatal T regulatory cell (T(reg)) frequency and function between infants from Western (Australia) and traditional (Papua New Guinea) environments.
- To investigate the impact of differing microbial exposures on early immune development.
- To test the hypothesis that Western environments lead to impaired neonatal T(reg) induction or function.
Main Methods:
- Comparison of cord blood samples from Australian (AUS) and Papua New Guinean (PNG) neonates.
- Quantification of neonatal T regulatory cells (T(reg)) using flow cytometry (CD4(+) Foxp3(+) CD127(-) CD25(+/high)).
- Assessment of T(reg) suppressive function through in vitro depletion and supplementation assays.
Main Results:
- Neonatal T regulatory cell (T(reg)) frequency was higher in Australian newborns compared to those from Papua New Guinea.
- Despite frequency differences, the suppressive function of a subset of cord T(reg) was qualitatively similar between the two groups.
- These findings did not support a hypothesis of poor T(reg) induction or function in Western environments.
Conclusions:
- The study's findings do not support the hypothesis that Western environments impair neonatal T regulatory cell (T(reg)) induction or function.
- Alternative mechanisms of environmentally-induced immuno-regulation may be present in infants from traditional, high-microbial-burden environments.
- Further research is warranted to explore these alternative immune regulation pathways in Papua New Guinean 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 (T(reg)). There is now increasing evidence that such conditioning begins in utero.
Methods:
We compared neonatal T(reg) 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 T(reg), defined as CD4(+) Foxp3(+) CD127(-) CD25(+/high) was found to be higher in the cord blood of AUS compared to PNG newborns. However, cord T(reg) suppressive function in a small subset of children was qualitatively similar between PNG and AUS newborns in both a T(reg) depletion assay and a T(reg) 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 T(reg). However, environmentally-induced immuno-regulation may potentially occur via alternative mechanisms in PNG newborns that should now be investigated further.
