Abstract 290: Upregulation Of Regulatory T Cells Improves Fetal Development In Preeclamptic Rat Model But Has No Influence On Hypertension And Proteinuria.

Abstract

Preeclampsia is characterized by hypertension, proteinuria and often associated with intrauterine growth retardation. There is a growing body of evidence that immunological dysregulation, involving T-cells, is implicated in causing preeclampsia. Proper recognition of paternal antigens by regulatory T cells is essential for successful outcome of pregnancy. The aim of the study was to evaluate the effect of upregulating regulatory T cells in an established transgenic rat model for preeclampsia. Application of CD28-superagonistic antibody has been shown to effectively upregulate regulatory T cells. In the first protocol (treatment arm) we applied 1mg of CD28-superagonist or control antibody on day 11 and 15 of pregnancy. In the second protocol (prevention arm) the superagonist or control antibody was applied on day 1, 5 and 9 to improve placentation with an upregulation of regulatory T cells at implantation site. Superagonist increased regulatory T cells in circulation and placenta from 1.6 ± 0.2% of CD4-positive T cells to 18.9 ± 4.8% and from 2.61 ± 0.96% to 23.27 ± 7.64%, respectively. Blood pressure (152.1 ± 5.8 mmHg vs 155.1 ± 3.6 mmHg, measured by telemetry on day 16) and albuminuria (30.6 ± 15.1 mg/d vs 14.6 ± 5.5 mg/d) were similar in the superagonist or sham treated preeclamptic group for both protocols. Rats treated with CD28-superagonist, showed higher pup weight (2.66 ± 0.03 g vs 2.37 ± 0.05 g) in preventive protocol and (3.04 ± 0.04 g vs 2.54 ± 0.1 g) in the treatment protocol. Intrauterine growth restriction, calculated by brain to liver weight ratio, was also decreased by superagonist in both protocols (0.88 ± 0.03 vs 1.07 ± 0.03 for prevention strategy and 0.72 ± 0.02 vs 1.05 ± 0.07 for therapeutic protocol respectively). Induction of regulatory T cells in circulation and uteroplacental unit early and late in an established preeclamptic rat model had no influence on hypertension and proteinuria. However, it improved the fetal outcome by ameliorating intrauterine growth retardation substantially.