An increased population of regulatory T cells improves the pathophysiology of placental ischemia in a rat model of preeclampsia

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2015-10, Vol.309 (8), p.R884-R891
• Main Authors: Cornelius, Denise C, Amaral, Lorena M, Harmon, Ashlyn, Wallace, Kedra, Thomas, Alexia J, Campbell, Nathan, Scott, Jeremy, Herse, Florian, Haase, Nadine, Moseley, Janae, Wallukat, Gerd, Dechend, Ralf, LaMarca, Babbette
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Blood Pressure; Cytokines - genetics; Cytokines - metabolism; Endothelin-1 - genetics; Endothelin-1 - metabolism; Female; Fluid and Electrolyte Homeostasis; Gene Expression Regulation; Hormones, Reproduction and Development; Ischemia - pathology; Oxygen; Placenta - blood supply; Placenta - cytology; Placenta - pathology; Pre-Eclampsia - pathology; Preeclampsia; Pregnancy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; T cell receptors; T-Lymphocytes, Regulatory - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00154.2015

The reduced uterine perfusion pressure (RUPP) rat model of preeclampsia exhibits much of the pathology characterizing this disease, such as hypertension, inflammation, suppressed regulatory T cells (TRegs), reactive oxygen species (ROS), and autoantibodies to the ANG II type I receptor (AT1-AA) during pregnancy. The objective of this study was to determine whether supplementation of normal pregnant (NP) TRegs into RUPP rats would attenuate the pathophysiology associated with preeclampsia during pregnancy. CD4(+)/CD25(+) T cells were isolated from spleens of NP and RUPP rats, cultured, and injected into gestation day (GD) 12 normal pregnant rats that underwent the RUPP procedure on GD 14. On GD 1, mean arterial pressure (MAP) was recorded, and blood and tissues were collected for analysis. One-way ANOVA was used for statistical analysis. MAP increased from 99 ± 2 mmHg in NP (n = 12) to 127 ± 2 mmHg in RUPP (n = 21) but decreased to 118 ± 2 mmHg in RUPP+NP TRegs (n = 17). Circulating IL-6 and IL-10 were not significantly changed, while circulating TNF-α and IL-17 were significantly decreased after supplementation of TRegs. Placental and renal ROS were 339 ± 58.7 and 603 ± 88.1 RLU·min(-1)·mg(-1) in RUPP and significantly decreased to 178 ± 27.8 and 171 ± 55.6 RLU·min(-1)·mg(-1), respectively, in RUPP+NP TRegs; AT1-AA was 17.81 ± 1.1 beats per minute (bpm) in RUPP but was attenuated to 0.50 ± 0.3 bpm with NP TRegs. This study demonstrates that NP TRegs can significantly improve inflammatory mediators, such as IL-17, TNF-α, and AT1-AA, which have been shown to increase blood pressure during pregnancy.