Abstract 064: CD4+ T Cells Mediate Pregnancy-induced Renal Damage In The Dahl SS In A Process Dependent Upon NADPH Oxidase 2 (NOX2)

Abstract

Previous work from our lab demonstrated that adoptive transfer of Dahl SS splenocytes into rats lacking T cells (SS CD247-/- ) led to significant renal damage and impairment in uterine artery blood flow during pregnancy. In contrast, transfer of SS p67phox-/- splenocytes, which lack the ability to generate NOX2-derived ROS, did not amplify pregnancy-induced renal damage. It is unknown what cell type in splenocytes mediates these effects. The present study tested the hypothesis that adoptive transfer of Dahl SS CD4+ T cells would induce a preeclamptic-like phenotype in the SS CD247-/- in a process dependent on NOX2. CD4+ T cells from Dahl SS or SS p67phox-/- were transferred into SS CD247-/- rats by intraperitoneal injection at postnatal day 5 to investigate the oxidative capacity of CD4+ T cells. Injected SS CD247-/- rats were aged to 10 weeks when they were mated with naïve littermate males. Prior to mating, baseline MAP and protein excretion rates were comparable between the groups (136±6 vs 134±3 mmHg, 33±5 vs 28±3 mg/day, p> 0.05, n=5/group, SS vs SS p67phox-/- , respectively). At the end of the pregnancy, the SS treated rats develop significant proteinuria that is not observed in the rats that received SS p67phox-/- CD4+ T cells (138±14 vs 83±16 mg/day, p< 0.05) despite no difference in MAP. In addition, there was an increase in uterine artery resistance index as assessed by Doppler ultrasound at GD20 in the SS treated relative to SS p67phox-/- (0.70±0.03 vs 0.62±0.02, p <0.05) indicating an impairment in blood flow leading to the placenta. There was a trending reduction in placental efficiency (fetal/placental weight) observed in the rats injected with SS CD4+ T cells versus those injected with SS p67phox-/- CD4+ T cells (3.99±0.3 vs 4.57±0.1, p=0.06) suggesting there is an impairment in placental function. Taken together, the present data suggest a causal role for NOX2 in CD4+ T cells in pregnancy-associated renal damage and impairment of vascular function.