Abstract P618: Foxp3+ Regulatory T cell Depletion Eliminates Ang II-Induced Hypertension Resistance in Female Mice
Compared to males, premenopausal females are resistant to the development of Ang II hypertension. In males, Ang II induces hypertension, in part, through mechanisms requiring T effector lymphocytes. Recently, our lab has demonstrated that females can prevent the T lymphocyte-dependent increase in blood pressure (SBP and MAP) and expression of pro-inflammatory cytokines in the kidney in response to Ang II infusion. Because Foxp3+ T regulatory cells suppress the pro-inflammatory and hypertensive actions of T effector cells, we sought to determine whether Foxp3+ T regulatory cells contribute to this resistance in females. Premenopausal (8 week old) 129SVE female mice were infused with Ang II (800ng/kg/min, 14d) and received 4 doses of the anti-CD25 antibody PC-61 to transiently deplete Foxp3+ T regulatory cells (every 84 hours beginning 12 hours prior to Ang II infusion, 250μg/dose, i.p., vehicle control). Blood pressure was measured before and after Ang II infusion via non-invasive tail cuff. Ang II induced a significant increase in systolic blood pressure in Foxp3+-depleted mice, while resistance was retained in vehicle-treated mice (Con Δ5 ± 5mmHg, Ang II Δ10 ± 7mmHg, PC-61 Δ28 ± 9*mmHg, *p<0.05 vs Con). Flow cytometric analysis demonstrated that PC-61-treatment significantly reduced the number of Foxp3+ splenic T cells compared to control (Con 1.7x106 cells, Ang II 2.3x106 cells, PC-61 8.3x105* cells, *P<0.05 vs Con) without changing CD3+ and CD4+ T cell counts. The number of Foxp3+ T cells residing in the kidney was also significantly reduced by PC-61 (Con 1,152 ± 368 cells, Ang II 686 ± 389 cells, PC-61 210 ± 35* cells, *P<0.05 vs Con). Quantitative real-time PCR demonstrated that whole kidney expression of MCP-1 and ENaC alpha were significantly increased in Foxp3+-depleted mice (MCP-1- Con 1.0 ± 0.1, Ang II 1.6 ± 0.4, PC-61 1.8 ± 0.2*; ENaC-α- Con 1.0 ± 0.1, Ang II 1.6 ± 0.2, PC-61 2.1 ± 0.1*, *P<0.05 vs Con). These data suggest that the anti-inflammatory Foxp3+ T regulatory cells play a significant role in mediating the resistance to Ang II hypertension in premenopausal female mice, and may influence renal inflammation and sodium retention during chronic Ang II infusion.
Author Disclosures: D. Pollow: None. M.J. Romero-Aleshire: None. J. Uhrlaub: None. J.P. Konhilas: None. J. Nikolich-Zugich: None. H.L. Brooks: None.
- © 2015 by American Heart Association, Inc.