|Understanding the Immune Microenvironment at the Uteroplacental Interface.|
In human pregnancy, the baby is 50% non-self, but is not rejected as an allogeneic organ transplant would be. The local interaction site between mother and baby is the uteroplacental interface (UPI), where maternal decidua develops between the uterus and the fetal placenta. We seek to understand the local immune microenvironment of the UPI to identify the critical factors mediating maintenance of maternal – fetal tolerance.
Using a novel, non-invasive sampling method, we isolated lymphocytes from the surgical sponge used to clean the uterus after C-section, and compared them to the peripheral blood (PB) of 3rd trimester healthy pregnant women.
The term UPI lymphocyte pool contained a similar proportion of CD3+ cells (~62%) vs. PB but within the CD3- fraction, NK cells were significantly enriched (CD56hiCD16- PB 1.86% +/- 0.36, UPI 19.84 +/- 3.14, p<0.0001. CD56loCD16+ PB 24.22 +/-4.15 UPI 50.53+/- 3.17 p<0.0001) while monocytes/macrophages were decreased (PB 22.64 +/- 1.43, UPI 6.05 +/- 0.95). Intracellular cytokines in gd T cells (IFNg, TNFa, and Granzyme A) and NK cells (Perforin A and Granzyme A) were significantly elevated at the UPI vs. PB. Further, CD56hi CD16- uterine NK cells but not PB NK cells exclusively displayed an activated (CD69+) phenotype and a significantly more of the apoptosis-inducing molecule Fas (mean PB 21.74 +/- 4.5; mean UPI 43.61 +/- 2.02 p=0.0007).
The dramatic differences in cell type proportions, phenotypes and functionality we observed between lymphocytes at the UPI vs PB indicate a specific local immune microenvironment that develops at the UPI. The signals – and mechanisms that attract and retain lymphocytes at the UPI are unknown but likely important for understanding of how the necessary tolerogenic environment for successful pregnancy is established and maintained.