Placental CD4+ T cells isolated from preeclamptic women cause preeclampsia-like symptoms in 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 from PE patient placentas cause PE symptoms during pregnancy compared to those from NP women. CD4+ T cells were isolated from placentas of PE and NP women using anti-CD4 magnetic separation, cultured in TexMACS medium at 37 °C in 5% CO2, and injected intraperitoneally into nude-athymic rats on day 12 of gestation. On day 18, carotid catheters were implanted and on day 19, mean arterial pressure (MAP) was measured and blood and tissues were collected. MAP was 125 ± 2 mmHg in rats with NP CD4+ T cells but increased to 140 ± 4 mmHg in rats with PE CD4+ T cells. Significant differences in circulating cytokines tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17) and soluble fms-like tyrosine kinase-1 (sFlt-1) were found with PE vs NP CD4+ T cells (TNF-α- PE = 167.4 pg/mL, NP = 79.4 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. In addition, renal cortical endothelin-1 (ET-1) mRNA expression increased 4.5 fold in rats with PE CD4+ T cells versus those receiving to NP CD4+ T cells. These data indicate an important role for placental PE CD4+ T cells to cause many characteristics of PE during pregnancy.