The role of thymus- and extrathymus-derived regulatory T cells in maternal-fetal tolerance

作者：Zhengjuan Li, Xinyuan Liang, Xiaowen Chen, Yuying Chen, Fang Wang, Shuoshi Wang, Yihong Liao, Liping Li · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1109352 · 被引用次数：10 · 研究领域：Reproductive System and Pregnancy、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Regulatory T (Treg) cells could be divided into thymus-derived Treg (tTreg) cells and peripherally derived Treg (pTreg) cells, and in vitro induced Treg (iTreg) cells. To date, the functions of tTreg versus pTreg and their relative contributions to maternal-fetal immune tolerance remain insufficiently defined due to a lack of a specific marker to distinguish tTreg cells from pTreg cells. In this study, we investigated the role of thymus- and extrathymus-derived Treg cells in pregnancy tolerance using transgenic ACT-mOVA , Foxp3 DTR and Foxp3 GFP mice, and Treg cell adoptive transfer, etc. We found that the frequencies of Treg cells in the thymus, spleen and lymph nodes (LNs) in either syngeneically- or allogeneically-mated pregnant mice were not different from non-pregnant mice. However, percentages of blood Treg cells in pregnant mice increased at mid-gestation, and percentages of decidua Treg cells in pregnant mice increased as the pregnancy progressed compared with non-pregnant mice, and were significantly higher in allogeneic mice than those in syngeneic group. Compared with syngeneic mice, levels of CCR2 and CCR6 on blood and decidua Treg cells and CCL12 in the decidua significantly increased in allogeneic mice. A surrogate fetal antigen mOVA that was recognized by naïve T cells from OT-IIFoxp3 GFP mice induced the generation of pTreg cells in vivo . Transfusion of thymus and spleen Treg cells significantly decreased diphtheria toxin (DT)-increased embryo resorption rate...