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Breast-Fed Neonates Show Increased Immune Tolerance Against Maternal Antigens

Authors
Hannah Wood, Richard Powell, Andrew Ewer, Paul Moss, Gergely Toldi

Institution(s)
1 – Department of Neonatology, Birmingham Women’s and Children’s NHS FT
2 – Institute of Immunology and Immunotherapy, University of Birmingham
3 – Institute of Metabolism and Systems Research, University of Birmingham

Introduction
In order to accommodate the developing fetus, a unique symbiosis must be maintained between the maternal and fetal immune systems during pregnancy. Therefore, the maternal immune system is known to be in a suppressed state during pregnancy. We hypothesized that immune suppression in pregnancy may be extended to the neonatal immune system in a bidirectional manner. Our study investigates the interaction of the maternal and neonatal immunological systems by analysing T cell responsiveness in the early postnatal period.

Methods
We collected cord blood (CB) samples from 37 healthy, term neonates delivered by elective Caesarean sections. A pre-delivery maternal peripheral blood sample was also obtained. All neonates were re-sampled for peripheral blood during a home visit at 3 weeks of age. T cells were isolated and mixed lymphocyte reactions (MLRs) were performed over 5 days (CB or neonatal responders versus maternal antigens and vice versa). In a subset of samples, MLRs were also studied following the depletion of CD25+ cells.

Results
Maternal T cells showed an increased response against neonatal antigens at 3 weeks compared to CB antigens. The neonatal T cell response against maternal antigens decreased by 3 weeks of age. However, this decrease was only observed in breast-fed (n=24), but not in exclusively formula-fed (n=13) infants. When CD25+ cells were depleted from the samples, an increase was observed in the response of maternal and neonatal T cells, but not that of CB T cells.

Conclusions
Although there was no evidence to support the original hypothesis of our study, we identified that breast-fed neonates show a decreased T cell response to maternal antigens at 3 weeks of age compared to birth. This decrease appears to be mediated by regulatory T cells and could be due to on-going antigen load via breastmilk and may reflect postnatal immune tolerance towards maternal antigens.

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