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

• Published in: Scientific reports Vol. 7; no. 1; pp. 2884 - 10
• Main Authors: Feyaerts, Dorien, Benner, Marilen, van Cranenbroek, Bram, van der Heijden, Olivier W. H., Joosten, Irma, van der Molen, Renate G.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.06.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 631/250/1619; 631/250/347; CD25 antigen; CD4 antigen; Cellular Microenvironment - immunology; Decidua; Decidua - immunology; Decidua - metabolism; Effector cells; Endometrium; Endometrium - immunology; Endometrium - metabolism; Female; Fetuses; Helper cells; Humanities and Social Sciences; Humans; Immune Tolerance; Immunological memory; Immunophenotyping; Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphocytes T; Memory cells; Menstruation; multidisciplinary; Peripheral blood mononuclear cells; Phenotype; Pregnancy; Pregnancy complications; Science; Science (multidisciplinary); T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Uterus; Uterus - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-03191-0

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 + CD25 high CD127 − 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.