Abstract P272: Preeclamptic Placental CD4+ T Cells Cause Preeclamptic Like Features in Normal Pregnant Nude Athymic Rats

Abstract

Preeclampsia (PE), new onset hypertension during pregnancy, is associated with a proinflammatory profile compared to normal pregnancy (NP). We hypothesize that CD4 + T cells play an important role to cause much of the pathophysiology associated with PE. To determine if CD4 + T cells isolated from PE patients cause PE symptoms during pregnancy compared to those collected from NP women, CD4 + T cells were isolated from placentas of both PE and NP women using magnetic separation with anti-CD4 antibodies, cultured in TexMACS medium with IL-2 at 37°C in 5% CO 2 , and injected intraperitoneally into pregnant, nude-athymic rats on day 12 of gestation. On day 18, carotid catheters were implanted and on day 19 MAP was measured and blood and tissues were collected. MAP was 125±3 mmHg in rats with NP T cells but increased to 140±9 mmHg in rats with PE T cells. Significant differences in circulating cytokines TNF-α, IL-6, IL-17 and sFlt-1 were found with PE vs NP CD4 + T cells (TNF-α- PE=142.4 pg/mL, NP=79.4 pg/mL; IL-6 - PE=311.6 pg/mL, NP=277.8 pg/mL; IL-17-PE= 7.054 pg/mL, NP=3.185 pg/mL; sFlt-1-PE=90.7 pg/mL, NP=58.2 pg/mL. However, there was no difference in Isoprostane levels or IL-2 between the two groups (Isoprostane-PE=3628 pg/mL, NP=3061 pg/mL; IL-2-PE=125 pg/mL, NP=125 pg/mL). ROS in tissues was measured using chemiluminescence and no difference was found in placenta while renal ROS showed an increased with PE CD4 + T cells vs NP CD4 + T cells (ROS-PE=5528 RLU/min/mg protein, NP=3372 RLU/min/mg protein). In addition, no difference in ET-1 mRNA was found in the placenta of nude rats receiving PE CD4+T cells, however, renal cortical ET-1 mRNA expression was increased 4.5 fold in rats with PE CD4+ T cells compared to those receiving to NP CD4+ T cells. These data indicate an important role for placental PE CD4 + T cells to cause inflammation and stimulate renal vasoactive pathways that may contribute to hypertension during pregnancy. This research is funded by R01HD067541-06