Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry

Abstract

During healthy pregnancy, a balanced microenvironment at the maternal-fetal interface with coordinated interaction between various immune cells is necessary to maintain immunological tolerance. While specific decidual immune cell subsets have been investigated, a system-wide unbiased approach is lacking. Here, mass cytometry was applied for data-driven, in-depth immune profiling of the total leukocyte population isolated from first, second, and third trimester decidua, as well as maternal peripheral blood at time of delivery. The maternal-fetal interface showed a unique composition of immune cells, different from peripheral blood, with significant differences between early and term pregnancy samples. Profiling revealed substantial heterogeneity in the decidual lymphoid and myeloid cell lineages that shape gestational-specific immune networks and putative differentiation trajectories over time during gestation. Uncovering the overall complexity at the maternal-fetal interface throughout pregnancy resulted in a human atlas that may serve as a foundation upon which comprehension of the immune microenvironment and alterations thereof in pregnancy complications can be built.

Human Tissue-Resident Memory T Cells in the Maternal–Fetal Interface. Lost Soldiers or Special Forces?

“…It is noteworthy that the authors used a very thorough approach and included PBMC reference samples in their mass spectrometry experiments, which greatly facilitates controlling for batch effects and other technical issues. Across term deliveries, an enrichment of memory T cells (delineated using CD45RO and CD45RA in conjunction) was observed in decidual tissues (both basalis and parietalis), which was greater than that observed in blood or early (first or second) trimester tissues [70]. Although not directly addressed, the data presented in this study further suggest many of these memory T cells are indeed Trm cells, as indicated by CD69 and PD-1 expression [70].…”

“…Although not directly addressed, the data presented in this study further suggest many of these memory T cells are indeed Trm cells, as indicated by CD69 and PD-1 expression [70]. Interestingly, these cells expressed additional activation markers: HLA-DR, ICOS, TIGIT, and CD39 [70]. As pointed out by the authors in their discussion, further studies are required to determine the significance and functional properties of these T cells.…”

“…Across term deliveries, an enrichment of memory T cells (delineated using CD45RO and CD45RA in conjunction) was observed in decidual tissues (both basalis and parietalis), which was greater than that observed in blood or early (first or second) trimester tissues [70]. Although not directly addressed, the data presented in this study further suggest many of these memory T cells are indeed Trm cells, as indicated by CD69 and PD-1 expression [70]. Interestingly, these cells expressed additional activation markers: HLA-DR, ICOS, TIGIT, and CD39 [70].…”

“…Transcriptomic studies of tissues from 6-14 weeks gestation echoed Trm findings, as SELL (encodes CD62L) transcripts were lower and CD69, PDCD1 (encodes PD-1), ITGA1 (encodes CD49a), and ITGAE (encodes CD103) were enriched in decidual T cells [11]. As pregnancy progresses and placental trophoblasts invade deeper into the maternal decidua, Trm cells appear to remain a sizable fraction of the immune infiltrate [61,69,70].…”

“…A recent study used mass cytometry to assess the immune landscape in first-, second-, and third-trimester decidua [70]. This study included paired decidua basalis and parietalis along with maternal blood for the third-trimester cohort.…”