Proliferation of endogenous regulatory T cells improve the pathophysiology associated with placental ischaemia of pregnancy


  • T. Ibrahim
  • L. Przybyl
  • A.C. Harmon
  • L.M. Amaral
  • J.L. Faulkner
  • D. Cornelius
  • M.W. Cunningham
  • T. Hünig
  • F. Herse
  • G. Wallukat
  • R. Dechend
  • B. LaMarca


  • American Journal of Reproductive Immunology


  • Am J Reprod Immunol 78 (5): e12724


  • PROBLEM: Preeclampsia (PE) is associated with inflammation and decreased Treg cells and IL-10. The reduced uterine perfusion pressure (RUPP) rat model of PE exhibits these characteristics, and we hypothesized that induction of endogenous Tregs by a specific stimulus (CD28 superagonistic monoclonal antibody) would reduce inflammation, vasoactive factors, and hypertension in RUPP rats. METHOD OF STUDY: RUPP was performed at gestation day (GD) 14; CD28 superagonist was administered intraperitoneally GD15; GD18 carotid catheters were inserted, and GD19 MAP and pup weight, blood, and tissues were collected. RESULTS: MAP (mmHg) in NP rats was 99+/-5 and 122±2 in RUPPs and was 111+/-1 mmHg in RUPP+SA. Circulating Tregs were 6±2% in NP rats and 0.77±0.49% in RUPP rats but increased to 11+/- 3% in RUPP+SA rats. Circulating IL-6 and IL-2 were decreased while IL-10 and TGF-B were significantly increased in RUPP+SA compared to RUPP controls. Vasoactive pathways such as ET-1, AT1-AA, and ROS were all reduced in RUPP+SA compared to RUPP. Pup weight was 2.4±0.05 mg in NP and 1.94+/-0.062 mg in RUPP and increased to 2.1+/-0.05 mg in RUPP+SA. CONCLUSION: These data suggest that stimulating endogenous Tregs lower factors causing hypertension and can improve fetal weight in response to PE.