Abstract-Angiotensin (Ang) II induces hypertension by mechanisms mediated in part by adaptive immunity and T effector lymphocytes. T regulatory lymphocytes (Tregs) suppress T effector lymphocytes. We questioned whether Treg adoptive transfer would blunt Ang II-induced hypertension and vascular injury. Ten-to 12-week-old male C57BL/6 mice were injected IV with 3ϫ10 5 Treg (CD4 ϩ CD25 ϩ ) or T effector (CD4 ϩ CD25 Ϫ ) cells, 3 times at 2-week intervals, and then infused or not with Ang II (1 g/kg per minute, SC) for 14 days. Ang II increased systolic blood pressure by 43 mm Hg (PϽ0.05), NADPH oxidase activity 1.5-fold in aorta and 1.8-fold in the heart (PϽ0.05), impaired acetylcholine vasodilatory responses by 70% compared with control (PϽ0.05), and increased vascular stiffness (PϽ0.001), mesenteric artery vascular cell adhesion molecule expression (2-fold; PϽ0.05), and aortic macrophage and T-cell infiltration (PϽ0.001). All of the above were prevented by Treg but not T effector adoptive transfer. Ang II caused a 43% decrease in

Aldosterone mediates actions of the renin-angiotensin-aldosterone system inducing hypertension, oxidative stress, and vascular inflammation. Recently, we showed that angiotensin II-induced hypertension and vascular damage are mediated at least in part by macrophages and T-helper effector lymphocytes. Adoptive transfer of suppressor T-regulatory lymphocytes (Tregs) prevented angiotensin II action. We hypothesized that Treg adoptive transfer would blunt aldosterone-induced hypertension and vascular damage. Thirteen to 15-week-old male C57BL/6 mice were injected intravenously at 1-week intervals with 3×10(5) CD4(+)CD25(+) cells (representing Treg) or control CD4(+)CD25(-) cells and then infused or not for 14 days with aldosterone (600 μg/kg per day, SC) while receiving 1% saline to drink. Aldosterone induced a small but sustained increase in blood pressure (P<0.001), decreased vasodilatory responses to acetylcholine by 66% (P<0.001), increased both media:lumen ratio (P<0.001) and media cross-sectional area of resistance arteries by 60% (P<0.05), and increased NADPH oxidase activity 2-fold in aorta (P<0.001), kidney and heart (P<0.05), and aortic superoxide production. As well, aldosterone enhanced aortic and renal cortex macrophage infiltration and aortic T-cell infiltration (all P<0.05), and tended to decrease Treg in the renal cortex. Treg adoptive transfer prevented all of the vascular and renal effects induced by aldosterone. Adoptive transfer of CD4(+)CD25(-) cells exacerbated aldosterone effects except endothelial dysfunction and increases in media:lumen ratio of resistance arteries. Thus, Tregs suppress aldosterone-mediated vascular injury, in part through effects on innate and adaptive immunity, suggesting that aldosterone-induced vascular damage could be prevented by an immunomodulatory approach.