Human uterine lymphocytes acquire a more experienced and tolerogenic phenotype during pregnancy

Abstract

Pregnancy requires a delicate immune balance that nurtures the allogeneic fetus, while maintaining reactivity against pathogens. Despite increasing knowledge, data is lacking on the transition of pre-pregnancy endometrial lymphocytes to a pregnancy state. Here, we immunophenotyped lymphocytes from endometrium (MMC), term decidua parietalis (DPMC), and PBMC for direct comparison. We found that the immune cell composition of MMC and DPMC clearly differ from each other, with less NK-cells, and more NKT-cells and T-cells in DPMC. An increased percentage of central memory and effector memory T-cells, and less naive T-cells in DPMC indicates that decidual T-cells are more experienced than endometrial T-cells. The increased percentage of CD4+CD25highCD127− Treg in DPMC, including differentiated Treg, is indicative of a more experienced and tolerogenic environment during pregnancy. The Th cell composition of both MMC and DPMC was different from PBMC, with a preference for Th1 over Th2 in the uterine environment. Between MMC and DPMC, percentages of Th cell subsets did not differ significantly. Our results suggest that already before pregnancy a tightly controlled Th1/Th2/Th17 balance is present. These findings create opportunities to further investigate the underlying immune mechanism of pregnancy complications using menstrual blood as a source for endometrial lymphocytes.

Alteration of the immune cell profiles in the pathophysiology of tubal ectopic pregnancy

“…Depletion of Tregs leads to pregnancy failure and autogenic Tregs transfusion into the uterus protects from fetal loss in abortion‐prone mice . Congruously, a higher number and percentage of tolerogenic CD4 + CD25 high Tregs has been detected in peripheral blood and term decidua parietalis of early pregnant women than that of non‐pregnant women, indicating that gestation promotes Treg expansion . Of note, the proportion of Tregs in the peripheral blood and the decidua is reduced in unexplained miscarriages .…”

Uterine B Cells Exhibit Regulatory Properties During the Peri-Implantation Stage of Murine Pregnancy

“…Uterine cell profiling of the murine estrous cycle showed that B cells constituted 1.5% of viable cells at estrus (12). In humans, B cells are considered rare lymphocyte subpopulations in the uterus with a median of 2% in pre-implantation uterine tissue and 5% in the decidua (13,14). Moreover, the functional promiscuity of B cells also poses an added layer of complexity in describing the specific role of B cells in pregnancy.…”

Innate and Adaptive Immune Responses in HELLP Syndrome

“…Moreover, the immunoglobulin levels of IgM, IgA, and IgG in the peripheral circulation are also increased in murine pregnancy in comparison to non-pregnant mice (129). Studies in humans reported that absolute counts of B cell peripheral compartment in the last trimester of pregnancy and in term decidua are decreased in comparison to non-pregnant controls (130,131). HELLP is not typically described as an autoimmune disorder, however, it is highly prevalent in pregnant women with autoimmune diseases such as acute phospholipid syndrome, systemic lupus erythematosus and thrombotic thrombocytopenic purpura (132)(133)(134)(135).…”