先充血（PE）是与激活的CD4+ T细胞和自身抗体靶向血管紧张素Ⅱ型1受体（AT1-AA）相关的妊娠高血压性疾病。我们之前已经显示，与正常孕妇（NP）相比，从PE患者分离的CD4+ T细胞注射到孕妇裸鼠身上，会导致高血压、增加肿瘤坏死因子α（TNF-α）、内皮素-1和类似于Fms样酪氨酸激酶-1的可溶性形式（sFlt-1）。然而，PE CD4+ T细胞作为引发高血压的AT1-AA机制的作用尚不清楚。目标：我们的目标是确定PE CD4+ T细胞是否能在孕妇裸鼠身上刺激AT1-AA的产生。从人类NP和PE胎盘中分离CD4+ T细胞，并在妊娠日（GD）12将其注射入裸鼠身体中。为了研究PE CD4+ T细胞刺激B细胞分泌AT1-AA的作用，接受PE CD4+ T细胞注射的一部分裸鼠在GD 14接受了利妥昔单抗的治疗，而GD 12接受了抗CD40配体（抗CD40L）的治疗。在GD 19，NP裸鼠+ PE CD4+ T细胞组的平均动脉压（MAP）和AT1-AA分别为[114 ± 1 mmHg（n = 9）]和[19.8 ± 0.9 bpm（n = 4）]，与NP裸鼠+ NP CD4+ T细胞（98 ± 2 mmHg（n = 7，P < 0.05）和1.3 ± 0.9 bpm（n = 5，P < 0.05））相比，均显著增加。利妥昔单抗（103 ± 2 mmHg，n = 3，P < 0.05）和抗CD40L（102 ± 1 mmHg，n = 3，P < 0.05）降低了MAP与NP裸鼠+ PE CD4+ T细胞组相比。PE CD4+ T细胞引发了外周增生诱导配体（APRIL）和胎盘血管紧张素转化酶2（ACE-2）活性的增加。这些结果表明胎盘CD4+ T细胞在PE的病理生理学中发挥了重要作用，通过激活分泌AT1-AA的B细胞在妊娠期引起高血压。

Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with activated CD4+ T cells and autoantibodies to angiotensin II type 1 receptor (AT1-AA). We have previously shown that CD4+ T cells isolated from women with PE cause hypertension, increased tumor necrosis factor alpha (TNF-α), endothelin-1, and soluble fms-like tyrosine kinase-1 (sFlt-1) when injected into pregnant nude-athymic rats compared to CD4+ T cells from normal pregnant (NP) women. However, the role of PE CD4+ T cells to cause AT1-AA as a mechanism of hypertension is not known. Aim: Our goal was to determine if PE CD4+ T cells stimulate AT1-AA in pregnant nude-athymic rats. CD4+ T cells were isolated from human NP and PE placentasand injected into nude-athymic rats on gestational day (GD) 12. In order to examine the role of the PE CD4+ T cells to stimulate B cell secretion of AT1-AA, a subset of the rats receiving PE CD4+ T cells were treated with rituximab on GD 14 or anti-CD40 ligand (anti-CD40L) on GD 12. On GD 19, mean arterial pressure (MAP) and tissues were obtained MAP [114 ± 1 mmHg (n = 9)] and AT1-AA [19.8 ± 0.9 beats per minute (bpm, n = 4)] were increased in NP nude + PE CD4+ T cells compared to NP nude + NP CD4+ T cells [98 ± 2 mmHg (n = 7, P < 0.05) and 1.3 ± 0.9 bpm (n = 5, P < 0.05)]. Rituximab (103 ± 2 mmHg, n = 3, P < 0.05) and anti-CD40L (102 ± 1 mmHg, n = 3, P < 0.05) lowered MAP compared to NP nude + PE CD4+ T cells. Circulating a proliferation-inducing ligand (APRIL) and placental angiotensin-converting enzyme 2 (ACE-2) activity was increased in response to PE CD4+ T cells. These results show that placental CD4+ T cells play an important role in the pathophysiology of PE, by activating B cells secreting AT1-AA to cause hypertension during pregnancy.