Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, Maryland, and Detroit, Detroit, Michigan, USA.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Am J Reprod Immunol. 2022 Nov;88(5):e13606. doi: 10.1111/aji.13606. Epub 2022 Sep 6.
Pregnancy represents a state of systemic immune activation that is primarily driven by alterations in circulating innate immune cells. Recent studies have suggested that cellular adaptive immune components, T cells and B cells, also undergo changes throughout gestation. However, the phenotypes and functions of such adaptive immune cells are poorly understood. Herein, we utilized high-dimensional flow cytometry and functional assays to characterize T-cell and B-cell responses in pregnant and non-pregnant women.
Peripheral blood mononuclear cells from pregnant (n = 20) and non-pregnant (n = 25) women were used for phenotyping of T-cell and B-cell subsets. T-cell proliferation and B-cell activation were assessed by flow cytometry after in vitro stimulation, and lymphocyte cytotoxicity was evaluated by using a cell-based assay. Statistical comparisons were performed with linear mixed-effects models.
Pregnancy was associated with modestly enhanced basal activation of peripheral CD4 T cells. Both CD4 and CD8 T cells from pregnant women showed increased activation-induced proliferation; yet, a reduced proportion of these cells expressed activation markers compared to non-pregnant women. There were no differences in peripheral lymphocyte cytotoxicity between study groups. A greater proportion of B cells from pregnant women displayed memory-like and activated phenotypes, and such cells exhibited higher activation following stimulation.
Maternal circulating T cells and B cells display distinct responses during pregnancy. The former may reflect the unique capacity of T cells to respond to potential threats without undergoing aberrant activation, thereby preventing systemic inflammatory responses that can lead to adverse perinatal consequences.
妊娠是一种全身性免疫激活状态，主要由循环固有免疫细胞的改变驱动。最近的研究表明，细胞适应性免疫成分，T 细胞和 B 细胞，在整个妊娠过程中也会发生变化。然而，这些适应性免疫细胞的表型和功能仍知之甚少。在此，我们利用高维流式细胞术和功能测定来描述妊娠和非妊娠妇女的 T 细胞和 B 细胞反应。
来自妊娠（n=20）和非妊娠（n=25）妇女的外周血单核细胞用于 T 细胞和 B 细胞亚群的表型分析。通过体外刺激后流式细胞术评估 T 细胞增殖和 B 细胞活化，通过基于细胞的测定评估淋巴细胞细胞毒性。采用线性混合效应模型进行统计比较。
妊娠与外周 CD4 T 细胞的基础激活适度增强相关。与非妊娠妇女相比，妊娠妇女的 CD4 和 CD8 T 细胞均表现出增强的激活诱导增殖；然而，这些细胞表达激活标志物的比例降低。研究组之间外周淋巴细胞细胞毒性无差异。来自妊娠妇女的更多 B 细胞显示记忆样和活化表型，并且这些细胞在刺激后表现出更高的活化。
母体循环 T 细胞和 B 细胞在妊娠期间表现出不同的反应。前者可能反映了 T 细胞对潜在威胁做出反应而不发生异常激活的独特能力，从而防止可能导致不良围产期后果的全身性炎症反应。
