Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3 Women's Centre, JR Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.
Nuffield Department of Obstetrics and Gynaecology, Oxford Fertility and Institute of Reproductive Sciences, University of Oxford, Level 3 Women's Centre, JR Hospital, Headley Way, Headington, Oxford, OX4 2HW, UK.
Sci Rep. 2017 Jan 23;7:41335. doi: 10.1038/srep41335.
When trying to conceive 1% of couples have recurrent miscarriages, defined as three or more consecutive pregnancy losses. This is not accounted for by the known incidence of chromosomal aneuploidy in miscarriage, and it has been suggested that there is an immunological aetiology. The endometrial mucosa is populated by a variety of immune cells which in addition to providing host pathogen immunity must facilitate pregnancy. Here we characterise the endometrial CD8-T cell population during the embryonic window of implantation and find that the majority of cells are tissue resident memory T cells with high levels of CD69 and CD103 expression, proteins that prevent cells egress. We demonstrate that unexplained recurrent miscarriage is associated with significantly decreased expression of the T-cell co-receptor CD8 and tissue residency marker CD69. These cells differ from those found in control women, with less expression of CD127 indicating a lack of homeostatic cell control through IL-7 signalling. Nevertheless this population is resident in the endometrium of women who have RM, more than three months after the last miscarriage, indicating that the memory CD8-T cell population is altered in RM patients. This is the first evidence of a differing pre-pregnancy phenotype in endometrial immune cells in RM.
当尝试怀孕时，1%的夫妇会反复流产，定义为连续三次或更多次妊娠丢失。这不能用已知的流产中染色体非整倍体的发生率来解释，有人认为这与免疫病因有关。子宫内膜黏膜中存在各种免疫细胞，除了提供宿主病原体免疫外，还必须促进妊娠。在这里，我们描述了胚胎着床窗口期的子宫内膜 CD8-T 细胞群，发现大多数细胞是组织驻留记忆 T 细胞，具有高水平的 CD69 和 CD103 表达，这些蛋白阻止细胞迁出。我们证明，不明原因的反复流产与 T 细胞共受体 CD8 和组织驻留标记物 CD69 的表达显著降低有关。这些细胞与在对照女性中发现的细胞不同，CD127 的表达较少表明通过 IL-7 信号缺乏稳态细胞控制。然而，这群细胞在 RM 女性的子宫内膜中仍然存在，在最后一次流产后三个月以上，这表明 RM 患者的记忆 CD8-T 细胞群发生了改变。这是首次在 RM 中发现子宫内膜免疫细胞在妊娠前表型上存在差异的证据。
