Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Obstetrics and Gynecology, Kirstein 3rd floor, Boston, MA, 02215, USA.
Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA.
Reprod Sci. 2023 Sep;30(9):2655-2664. doi: 10.1007/s43032-023-01165-4. Epub 2023 Feb 7.
Conventional and regulatory T cells (Treg) are dynamic mediators of maternal immune tolerance to the developing feto-placental unit. Functional evaluation of T cells at the maternal-fetal interface is crucial to elucidate the immunologic basis of obstetric complications. Our objective was to define the T cell phenotype and function of uterine intervillous blood (IVB) in pregnancy with and without preeclampsia. We hypothesize that preeclampsia is associated with impaired immune tolerance and a pro-inflammatory uterine T cell microenvironment. In this cross-sectional study, maternal peripheral blood (PB) and uterine IVB (obtained from the surgical sponge used to clean the placental bed during cesarean delivery) were collected from participants with and without preeclampsia. Proportion, activation, and cytokine production of T cell subsets were quantified by flow cytometry. T cell parameters were compared by tissue source and by preeclampsia status. Sixty participants, 26 with preeclampsia, were included. Induced Treg made up a greater proportion of IVB T cells compared to PB and had greater cytokine-producing capacity. Preeclampsia was associated with increased ratio of pro-inflammatory IL-17α to suppressive IL-10 cytokine production by CD4 T cell subsets in IVB, but not in PB. Human uterine IVB is composed of activated, cytokine-producing T cell subsets distinct from maternal PB. Preeclampsia is associated with a pro-inflammatory IVB profile, with increased IL-17α /IL-10 ratio in all CD4 T cell subsets. IVB sampling is a useful tool for investigating human T cell biology at the maternal-fetal interface that may inform immunotherapeutic strategies for preeclampsia.
常规和调节性 T 细胞（Treg）是母体对发育中的胎-胎盘单位免疫耐受的动态介质。在母体-胎儿界面对 T 细胞进行功能评估对于阐明产科并发症的免疫学基础至关重要。我们的目的是定义患有和不患有子痫前期的妊娠期间子宫绒毛间隙血（IVB）中的 T 细胞表型和功能。我们假设子痫前期与免疫耐受受损和促炎的子宫 T 细胞微环境有关。在这项横断面研究中，从患有和不患有子痫前期的参与者中收集了母体外周血（PB）和子宫 IVB（从剖宫产时用于清洁胎盘床的手术海绵中获得）。通过流式细胞术定量 T 细胞亚群的比例、激活和细胞因子产生。通过组织来源和子痫前期状态比较 T 细胞参数。共纳入 60 名参与者，其中 26 名患有子痫前期。与 PB 相比，IVB T 细胞中诱导的 Treg 占更大比例，且具有更大的细胞因子产生能力。与 PB 相比，子痫前期与 IVB 中 CD4 T 细胞亚群促炎的白细胞介素-17α与抑制性白细胞介素-10 细胞因子产生的比例增加有关，但在 PB 中没有。人类子宫 IVB 由与母体 PB 不同的活化、产生细胞因子的 T 细胞亚群组成。子痫前期与 IVB 中促炎特征相关，所有 CD4 T 细胞亚群中白细胞介素-17α/白细胞介素-10 比值增加。IVB 采样是研究母体-胎儿界面人类 T 细胞生物学的有用工具，可能为子痫前期的免疫治疗策略提供信息。
