Abstract P178: Depletion of Gamma-Delta T Cells Protects Against Toll-Like Receptor-Induced Preeclampsia in Mice
Preeclampsia (PE), a hypertensive disorder of pregnancy, is associated with vascular endothelial dysfunction and excessive immunity and inflammation. However, it is unclear which innate immune cells propagate the pro-inflammatory state. Gamma-delta T (gdT) cells can secrete tolerogenic anti-inflammatory cytokines or cytotoxic pro-inflammatory cytokines depending on their activation status. gdT cells from women with PE produce significantly more IFNg and perforin and are less susceptible to apoptosis than gdT cells from normal pregnant women. We hypothesized that Toll-like receptor (TLR) activation in gdT cells induces inflammation and causes PE-like features in mice and that gdT cell KO mice would be resistant to developing TLR-induced PE-like features. Activation of splenocytes isolated from day 14 normal pregnant mice with the TLR3 agonist poly I:C or the TLR7 agonist R837 for 24 hours significantly increased gdT cells as well as IFNg and TNFa production. We have reported that poly I:C or R837 treatment of normal pregnant mice elicits a pregnancy-dependent PE-like syndrome by inducing a pro-inflammatory immune response. Pregnant poly I:C-treated and R837-treated mice had significantly increased splenic levels of gdT cells and plasma levels of IFNg and TNFa compared to pregnant vehicle-treated mice. Pregnant gdT cell KO mice treated with poly I:C or R837 did not develop hypertension or endothelial dysfunction. These data demonstrate that gdT cells mediate the TLR-induced PE-like features in mice and depletion of gdT cells may reduce the severity of PE in women.
Author Disclosures: K.R. Bounds: None. V.L. Chiasson: None. R.P. Tobin: None. M.K. Newell-Rogers: G. Consultant/Advisory Board; Significant; VG Life Sciences Inc. B.M. Mitchell: G. Consultant/Advisory Board; Significant; VG Life Sciences Inc.
This research has received full or partial funding support from the American Heart Association, South Central Affiliate (Arkansas, New Mexico, Oklahoma & Texas).
- © 2015 by American Heart Association, Inc.