# Myeloid-T cell proximity is prominent in healthy pregnancies with extreme fetal-maternal HLA incompatibility

## TL;DR

This study explores how the immune system adapts during high-risk pregnancies with significant genetic differences between mother and fetus.

## Contribution

The study reveals the role of myeloid cells and T cell proximity in maintaining immune tolerance in high HLA-mismatch pregnancies.

## Key findings

- Decidual myeloid cells make up 65% of immune cells and include 12 distinct clusters.
- Healthy OD pregnancies show increased CD163+HLA-DR+ myeloid cells and Tregs near T cells.
- Pre-eclampsia is marked by inflammation and oxidative stress gene imbalances.

## Abstract

Pregnancy requires local immune tolerization. Oocyte donation (OD) pregnancies, with extensive fetal-maternal human leukocyte antigen (HLA) mismatching, are at higher risk of pre-eclampsia. We hypothesize that immune adaptations are needed at the fetal-maternal interface to maintain healthy pregnancy despite high HLA dissimilarity. By multispectral imaging, myeloid cells constituted 65% of the decidual immune cells and encompassed 12 distinct clusters. Fully-allogeneic healthy OD pregnancies displayed a higher frequency of CD163+HLA-DR+ myeloid cells and FoxP3+CD4+ Tregs near CD4+ T cells compared to semi-allogeneic healthy pregnancies and pre-eclampsia, together with a Treg-reinforcing gene signature. Contrastingly, pre-eclampsia was characterized by enhanced inflammatory chemokine expression and oxidative-stress-gene imbalance. Pregnancy outcomes were unaffected by decidual pathology, maternal HLA antibodies, or fetal HLA-C/maternal KIR haplotypes. This study highlights the frequency, phenotypic diversity, and T cell proximity of decidual myeloid cells in OD pregnancies and suggests their immune regulatory effects to compensate for higher fetal-maternal HLA mismatch loads.

•Decidual myeloid cells dominate immune landscape in oocyte donation pregnancies•Myeloid-T cell proximity reflects tolerance in high HLA-mismatch OD pregnancies•Healthy OD pregnancies display Treg gene signature and reduced inflammation•Pre-eclamptic OD pregnancies show inflammatory and oxidative stress dysregulation

Decidual myeloid cells dominate immune landscape in oocyte donation pregnancies

Myeloid-T cell proximity reflects tolerance in high HLA-mismatch OD pregnancies

Healthy OD pregnancies display Treg gene signature and reduced inflammation

Pre-eclamptic OD pregnancies show inflammatory and oxidative stress dysregulation

Immunology; Pregnancy; Omics