Department of Medicine, Georgia Health Sciences University, Augusta, USA.
Am J Physiol Regul Integr Comp Physiol. 2012 Aug 15;303(4):R359-67. doi: 10.1152/ajpregu.00246.2012. Epub 2012 Jul 3.
T cells contribute to hypertension in male experimental models; data in females is lacking even though women are more likely to develop immune disorders. The goal of this study was to determine whether immune cells contribute to hypertension in female spontaneously hypertensive rats (SHR) and define the T cell profile in whole blood and kidneys of male and female SHR. We hypothesized that inflammatory cells contribute to hypertension in female SHR; however, male SHR have a higher blood pressure so we hypothesize they will have a heightened inflammatory profile. The lymphocyte inhibitor mycophenolate mofetil (MMF) was administered in a dose-dependent manner to SHR. At the highest dose (50 mg·kg(-1)·day(-1)), blood pressure was significantly decreased in both sexes, yet the percent decrease in blood pressure was greater in females (female: 12 ± 1%; males: 7 ± 1%, P = 0.01). Circulating and renal T cell profiles were defined using analytical flow cytometry. Female SHR had more circulating CD3(+), CD4(+), and pro-inflammatory CD3(+)CD4(+)RORγ(+) Th17 cells, whereas males had more immune-suppressive CD3(+)CD4(+)Foxp3(+) T regulatory cells. In the kidney, females had greater numbers of CD8(+) and T regulatory cells than males, whereas males had greater CD4(+) and Th17 cell infiltration. MMF decreased circulating and renal T cells in both sexes (P < 0.0001), although the effect of MMF on T cell subtypes was sex specific with females having greater sensitivity to MMF-induced decreases in lymphocytes. In conclusion, there is a lymphocyte contribution to the maintenance of hypertension in the female SHR and sex of the animal impacts the T cell profile.
T 细胞有助于雄性实验模型中的高血压;尽管女性更有可能患上免疫紊乱,但女性的数据却缺乏。本研究的目的是确定免疫细胞是否有助于雌性自发性高血压大鼠(SHR)中的高血压,并确定雄性和雌性 SHR 全血和肾脏中的 T 细胞特征。我们假设炎症细胞有助于雌性 SHR 中的高血压;然而,雄性 SHR 的血压更高,因此我们假设它们会有更高的炎症特征。淋巴细胞抑制剂霉酚酸酯(MMF)以剂量依赖性方式施用于 SHR。在最高剂量(50mg·kg(-1)·day(-1))时,两性的血压均显著降低,但女性的血压降低幅度更大(女性:12±1%;男性:7±1%,P=0.01)。使用分析流式细胞术定义循环和肾脏 T 细胞特征。雌性 SHR 具有更多的循环 CD3(+)、CD4(+)和促炎 CD3(+)CD4(+)RORγ(+)Th17 细胞,而雄性具有更多的免疫抑制性 CD3(+)CD4(+)Foxp3(+)T 调节细胞。在肾脏中,雌性的 CD8(+)和 T 调节细胞比雄性多,而雄性的 CD4(+)和 Th17 细胞浸润更多。MMF 减少了两性的循环和肾脏 T 细胞(P<0.0001),尽管 MMF 对 T 细胞亚型的作用具有性别特异性,女性对 MMF 诱导的淋巴细胞减少更敏感。总之,淋巴细胞有助于维持雌性 SHR 中的高血压,并且动物的性别会影响 T 细胞特征。