Department of Medical Biology, School of Medicine, Erciyes University, Kayseri, Turkey.
Betül-Ziya Eren Genome and Stem Cell Center (GENKOK), Kayseri, Turkey.
Am J Reprod Immunol. 2022 Jul;88(1):e13555. doi: 10.1111/aji.13555. Epub 2022 May 1.
Although pregnant women with gestational diabetes (GD), morbidly adherent placenta (MAP), and pregnancy hypertension (pHT) diseases lead to intrauterine growth restriction (IUGR), little is known about their effect on mucosal-associated invariant T (MAIT) and innate lymphoid cells (ILC) in the umbilical cord. This study aimed to quantify and characterize MAIT cells and ILCs in the cord blood of pregnant women with GD, MAP, and pHT diseases.
Cord blood mononuclear cells (CBMCs) were isolated by Ficoll-Paque gradient. CD3 TCRVα7.2 CD161 cells and ILC subsets were quantified by flow cytometry. CBMCs were stimulated with PMA/Ionomycin and Golgi Plug for 4 h and stained for IFN-γ, TNF-α, and granzyme B. The stained cells were analyzed on FACS ARIA III.
Compared with healthy pregnancies, in the cord blood of the pHT group, elevated number of lymphocytes was observed. Moreover, the absolute number of IFN-γ producing CD4 or CD4 subsets of CD3 TCRVα7.2 CD161 cells as well as those producing granzyme B were significantly elevated in the pHT group compared to healthy controls suggesting increased MAIT cell activity in the pHT cord blood. Similarly, in the MAP group, the absolute number of total CD3 TCRVα7.2 CD161 cells, but not individual CD4 or negative subsets, were significantly increased compared with healthy controls' cord blood. Absolute numbers of total CD3 TCRVα7.2 CD161 cells and their subsets were comparable in the cord blood of the GD group compared with healthy controls. Finally, the absolute number of total ILCs and ILC3 subset were significantly elevated in only pHT cord blood compared with healthy controls. Our data also reveal that IFN-γ or granzyme B cell numbers negatively correlated with fetal birth weight.
CD3 TCRVα7.2 CD161 cells and ILCs show unique expansion and activity in the cord blood of pregnant women with distinct diseases causing IUGR and may play roles in fetal growth restriction.
尽管患有妊娠糖尿病（GD）、黏附性胎盘（MAP）和妊娠高血压（pHT）疾病的孕妇会导致宫内生长受限（IUGR），但人们对这些疾病如何影响脐带中的黏膜相关不变 T（MAIT）和固有淋巴细胞（ILC）知之甚少。本研究旨在定量和分析患有 GD、MAP 和 pHT 疾病的孕妇脐带血中的 MAIT 细胞和 ILC。
通过 Ficoll-Paque 梯度分离脐带血单核细胞（CBMC）。通过流式细胞术定量 CD3 TCRVα7.2 CD161 细胞和 ILC 亚群。用 PMA/离子霉素和 Golgi Plug 刺激 CBMC 4 小时，并用 IFN-γ、TNF-α 和颗粒酶 B 染色。用 FACS ARIA III 分析染色细胞。
与健康妊娠相比，pHT 组脐带血中观察到淋巴细胞数量增加。此外，与健康对照组相比，pHT 组 CD3 TCRVα7.2 CD161 细胞产生 IFN-γ 的 CD4 或 CD4 亚群以及产生颗粒酶 B 的细胞绝对数明显增加，表明 pHT 脐带血中的 MAIT 细胞活性增加。同样，在 MAP 组中，与健康对照组的脐带血相比，总 CD3 TCRVα7.2 CD161 细胞的绝对数，但不是单个 CD4 或阴性亚群，明显增加。与健康对照组相比，GD 组脐带血中总 CD3 TCRVα7.2 CD161 细胞及其亚群的绝对数相当。最后，只有 pHT 脐带血中的总 ILC 和 ILC3 亚群的绝对数明显高于健康对照组。我们的数据还表明，IFN-γ 或颗粒酶 B 细胞数与胎儿出生体重呈负相关。
CD3 TCRVα7.2 CD161 细胞和 ILC 在导致 IUGR 的不同疾病孕妇的脐带血中表现出独特的扩增和活性，可能在胎儿生长受限中发挥作用。
