Abstract 294: CD4 + T cells Isolated from Preeclamptic Women Produce a Preeclampsia-Like Phenotype in Pregnant Nude-Athymic Rats

Abstract

Preeclampsia (PE) is the development of hypertension, with proteinuria, during the second half of pregnancy and is associated with an altered immune function, resulting in a chronic state of inflammation, which is believed to play an important role to increase vasoconstrictors such as Endothelin (ET-1) and autoantibodies as well as much of the pathophysiology associated with PE. It has been previously shown that women with PE have an altered CD4 + T cell population compared to normal pregnant women. In addition, Ana Zenclussen’s lab has shown that adoptive transfer of activated T helper 1 like splenocytes increased blood pressure, fetal rejection and cytokines secreted from uterine cells when transferred to normal pregnant mice. However, mechanisms causing the increased blood pressure and renal abnormalities were not further investigated. The purpose of this study was to determine if CD4 + T cells isolated from placentas of PE patients have altered consequences during pregnancy compared to those collected from normal pregnant (NP) women that may further define their role in causing the pathophysiology of PE. CD4 + T cells were isolated from placentas of PE and NP women, using magnetic anti-CD4 antibodies, cultured in TexMACS medium (Miltenyi Biotec) with IL-2 at 37°C in 5% CO 2 , and injected intraperitoneally into first timed 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 significantly increased from 125±3 mmHg in rats injected with NP CD4 + T cells to 140±9 mmHg in rats injected with PE CD4 + T cells. Circulating inflammatory cytokines IL-6 and TNF-α were measured and found to be increased in rats exposed to 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). Renal cortical ET-1 mRNA expression was found to be increased 4.5 fold in rats exposed to PE CD4+ T cells compared to those exposed to NP CD4+ T cells (p=0.06). These data suggest an important role for placental CD4 + T cells stimulated in women with PE to cause hypertension and inflammation and renal abnormalities during the course of this disease.