Presented at the Neonatal Society 2018 Summer Meeting.
Toldi G1,2, Powell RM2, Lissauer D1,2, Moss P2, Ewer AK1,2
1 Birmingham Women’s and Children’s Hospital, Birmingham, UK
2 University of Birmingham, Birmingham, UK
Background: Sepsis is responsible for up to 30% of global neonatal mortality. Although neonatal infections present an enormous global burden for healthcare, the only treatment option currently available is antibiotic therapy. Very little is known about the normal function of the neonatal immune system and this knowledge is critical for the identification of potential factors that might be amenable to medical support during periods of infection. We hypothesized that the feto-maternal immunological symbiosis requires adaptation of not only the maternal, but also the fetal immune system, which might itself be partially regulated by maternal factors.
Methods: We enrolled 8 women with healthy, uncomplicated pregnancies undergoing an elective Caesarean section. Maternal peripheral blood was taken before the section and cord blood samples were collected. A peripheral blood sample was also collected from neonates at three weeks of age. T cells were isolated from the samples and mixed lymphocyte reactions were performed over five days (maternal versus cord blood or neonatal cells and cord blood or neonatal versus maternal cells). Proliferation was measured by flow cytometry in the CD3, CD4 and CD8 subsets.
Results: An increased rate of proliferation was observed in maternal cells when incubated with neonatal cells compared to cord blood cells, most pronounced in the CD4 subset (CD3 cells: 2.85% vs 24.40%, CD4 cells: 2.75% vs 24.85%, CD8 cells: 0.55% vs 12.1%). On the contrary, proliferation of cord blood/neonatal cells was reduced at three weeks of age compared to birth, most pronounced in the CD8 subset (CD3 cells: 19.35% vs 8.5%, CD4 cells: 23.7% vs 14.65%, CD8 cells: 16.65% vs 0.75%).
Conclusion: The pregnancy-induced maternal immunosuppression towards fetal antigens appears to be diminished by three weeks post delivery (although it is not completely resolved). Surprisingly, neonatal T cells demonstrate decreased proliferation in the presence of maternal antigens three weeks after delivery compared to at birth. This is in line with the increased susceptibility to infection in the neonatal period, but does not confirm the notion that maternal factors induce neonatal immunosuppression or that the pregnancy-specific immunosuppression is extended into the fetal immune system.
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