Division of Inflammation and Infection (II), Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Division of Obstetrics and Gynecology, and Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden.
Front Immunol. 2021 Aug 9;12:718168. doi: 10.3389/fimmu.2021.718168. eCollection 2021.
Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset with proinflammatory and cytotoxic effector functions. During pregnancy, modulation of the maternal immune system, both at the fetal-maternal interface and systemically, is crucial for a successful outcome and manifests through controlled enhancement of innate and dampening of adaptive responses. Still, immune defenses need to efficiently protect both the mother and the fetus from infection. So far, it is unknown whether MAIT cells are subjected to immunomodulation during pregnancy, and characterization of decidual MAIT cells as well as their functional responses during pregnancy are mainly lacking. We here characterized the presence and phenotype of Vα7.2CD161 MAIT cells in blood and decidua (the uterine endometrium during pregnancy) from women pregnant in the 1 trimester, , the time point when local immune tolerance develops. We also assessed the phenotype and functional responses of MAIT cells in blood of women pregnant in the 3 trimester, , when systemic immunomodulation is most pronounced. Multi-color flow cytometry panels included markers for MAIT subsets, and markers of activation (CD69, HLA-DR, Granzyme B) and immunoregulation (PD-1, CTLA-4). MAIT cells were numerically decreased at the fetal-maternal interface and showed, similar to other T cells in the decidua, increased expression of immune checkpoint markers compared with MAIT cells in blood. During the 3 trimester, circulating MAIT cells showed a higher expression of CD69 and CD56, and their functional responses to inflammatory (activating anti-CD3/CD28 antibodies, and IL-12 and IL-18) and microbial stimuli (, group B streptococci and influenza A virus) were generally increased compared with MAIT cells from non-pregnant women, indicating enhanced antimicrobial defenses during pregnancy. Taken together, our findings indicate dual roles for MAIT cells during pregnancy, with an evidently well-adapted ability to balance the requirements of immune tolerance in parallel with maintained antimicrobial defenses. Since MAIT cells are easily activated, they need to be strictly regulated during pregnancy, and failure to do so could contribute to pregnancy complications.
黏膜相关恒定 T（MAIT）细胞是一种先天样 T 细胞亚群，具有促炎和细胞毒性效应功能。在怀孕期间，母体免疫系统在胎儿-母体界面和全身的调节对于成功的结果至关重要，表现为先天免疫的增强和适应性反应的抑制。尽管如此，免疫防御仍需要有效地保护母亲和胎儿免受感染。到目前为止，尚不清楚 MAIT 细胞在怀孕期间是否受到免疫调节，以及描述蜕膜 MAIT 细胞及其在怀孕期间的功能反应主要是缺乏的。我们在这里描述了在怀孕 1 个月末（局部免疫耐受发展的时间点）的孕妇血液和蜕膜（怀孕期间的子宫子宫内膜）中 Vα7.2CD161 MAIT 细胞的存在和表型。我们还评估了怀孕 3 个月末（全身免疫调节最为明显的时间点）孕妇血液中 MAIT 细胞的表型和功能反应。多色流式细胞术面板包括 MAIT 亚群的标记物，以及激活（CD69、HLA-DR、颗粒酶 B）和免疫调节（PD-1、CTLA-4）的标记物。在胎儿-母体界面处 MAIT 细胞数量减少，并且与蜕膜中的其他 T 细胞相似，与血液中的 MAIT 细胞相比，其免疫检查点标记物的表达增加。在 3 个月末，循环 MAIT 细胞表现出更高的 CD69 和 CD56 表达，并且它们对炎症（激活的抗-CD3/CD28 抗体以及 IL-12 和 IL-18）和微生物刺激（B 组链球菌和流感 A 病毒）的功能反应与非孕妇相比普遍增加，表明怀孕期间增强了抗微生物防御。总之，我们的发现表明 MAIT 细胞在怀孕期间具有双重作用，具有明显适应平衡免疫耐受要求的能力，同时保持抗微生物防御。由于 MAIT 细胞容易被激活，因此在怀孕期间需要严格调节，否则可能导致妊娠并发症。
