Prevention of T Cell Activation in Response to Placental Ischemia Improves Hypertension and Natural Killer Cell Number During Pregnancy

Abstract

Preeclampsia (PE), new onset hypertension during pregnancy, is the leading cause of death and morbidity world‐wide for the mother and fetus during pregnancy. The Reduced Uterine Perfusion Pressure Rat Model of Preeclampsia (RUPP) exhibits many characteristics of PE including hypertension, suppressed regulatory T cells (TRegS) associated with increased CD4+ T cells and B cells secreting agonistic autoantibodies to the AngII receptor (AT1‐AA). We have previously shown that blockade of T‐helper cells improves blood pressure and lowers AT1‐AA secretion. A potential mechanism for the decreased blood pressure is decreased cytolytic natural killer (cNK) cells. Abatacept is a fusion molecule designed to inhibit T cell co‐stimulation in response to antigens and is used to treat autoimmune diseases. We hypothesize that treatment with Abatacept will prevent the activation of T‐helper cells and therefore lower AT1‐AA as a mechanism to lower the activity of NK cells in response to placental ischemia in RUPP rats. Abatacept was given on day 13 via the jugular vein. On day 19, blood and tissues were collected, blood pressure (MAP), pup weight and NK cells were measured by flow cytometry in the blood and placenta. A one‐way ANOVA was used for statistical analysis. On GD19, MAP significantly increased in RUPP 119±2 mmHg (n=7, p<0.05) compared to NP controls 101±2 mmHg (n=7) and was normalized with abatacept (100±2.02 mmHg (n=10, p<0.05). Compared to the NP controls (2.216±0.054, n=7), pup weight significantly decreased in RUPP (1.919±0.113, n=7, p<0.05) and was 1.934± 0.050, with Abatacept (n=10, p<0.05). Circulating and placental total NK cells were 45±9, 59±11 % gate in NP rats (n=7, n=5), 59±4, 72±13 % gate in RUPP rats (n=7, n=4), which significantly decreased to 32±7, 25±9 % gate with Abatacept (n=10, p<0.05; n=10, p<0.05). Our findings indicate that prevention of T cell activation lowers total NK cell number and blood pressure in response to placental ischemia of pregnancy.Support or Funding Information2R01HD067541P20GM121334 T32HL105324