Abstract 14896: In Vivo Induction of Regulatory T Cells Delays the Development of Hypertension in Stroke-Prone Spontaneously Hypertensive Rats
Background: T cell activation is implicated in the pathogenesis of hypertension and its complications. In contrast, regulatory T (Treg) cells, which control the immune system, are reported to prevent angiotensin II-induced hypertension and cardiac damage. The precise role of Treg cells in the pathological process of hypertension, however, remains unclear. Recent studies demonstrated that interleukin (IL)-2 and anti-IL-2 monoclonal antibody (IL-2/mAb) complex selectively induces Treg cells in vivo. Here we aimed to determine whether Treg cells are decreased in genetically spontaneously hypertensive rats compared with normotensive rats, and if so, to examine whether administration of IL-2/mAb complex affects the development of hypertension and the progression of cardiac hypertrophy.
Methods and Results: We examined Treg cells in stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar-Kyoto rats (WKY). CD4+CD25+Foxp3+ cells (Treg cells) in the spleen and peripheral blood were significantly decreased in SHRSP compared with WKY at 5 weeks of age (before the onset of hypertension; %CD25+Foxp3+ gated on CD4+ cells in the spleen: 7.7±0.5 vs. 5.5±0.3, n=5/group, p<0.01; blood: 6.7±0.7 vs. 3.4±0.8, n=4/group, p<0.01), and at 15 weeks of age (established hypertensive stage; spleen: 9.9±0.7 vs. 5.4±0.4, n=4/group, p<0.01; blood: 8.8±0.7 vs. 4.5±0.1, n=4/group, p<0.001), whereas there was no difference between groups at 3 weeks of age. Administration of IL-2/mAb complex to young prehypertensive SHRSP selectively induced Treg cells in the spleen and peripheral blood within 4 weeks after treatment (spleen: 5.5±0.1 vs. 7.5±0.2, p<0.0001; blood: 3.4±0.1 vs. 4.3±0.2, p<0.01, n=5/group). IL-2/mAb complex therapy in SHRSP delayed the development of hypertension, and reduced the heart weight/body weight ratio (4.64±0.06 vs. 4.25±0.05 mg/g, p<0.01, n=5/group) and the cross-sectional area of cardiac myocytes (580±3.91 vs. 438±4.43 μm2, p<0.0001, n=5/group).
Conclusion: Our findings indicate that a decrease in Treg cells plays a crucial role in the pathological process of hypertension and cardiac hypertrophy in SHRSP. These findings may provide for potential immunomodulatory approach to prevent hypertension.
Author Disclosures: M. Katsuki: None. Y. Hirooka: None. T. Kishi: None. K. Sunagawa: None.
- © 2014 by American Heart Association, Inc.