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International Journal of Hypertension
Volume 2014 (2014), Article ID 126365, 12 pages
http://dx.doi.org/10.1155/2014/126365
Research Article

Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening

1Saver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
2Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
3Department of Physiology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
4Department of Pediatrics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
5Department of Surgery, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA
6Arizona Health Sciences Center, Room 4402, 1501 North Campbell Avenue, Tucson, AZ 85724, USA

Received 13 June 2014; Accepted 24 July 2014; Published 2 September 2014

Academic Editor: Tomohiro Katsuya

Copyright © 2014 Beenish Majeed et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Adaptive immune function is implicated in the pathogenesis of vascular disease. Inhibition of T-lymphocyte function has been shown to reduce hypertension, target-organ damage, and vascular stiffness. To study the role of immune inhibitory cells, CD4+CD25+Foxp3+ regulatory T cells (Tregs), on vascular stiffness, we stimulated the proliferation of Treg lymphocytes in vivo using a novel cytokine immune complex of Interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody clone JES6-1 (). Three-month-old male C57BL/6J mice were treated with IL-2/ concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val5]angiotensin II. Our results indicate that the IL-2/ complex effectively induced Treg phenotype expansion by 5-fold in the spleens with minimal effects on total CD4+ and CD8+ T-lymphocyte numbers. The IL-2/ complex inhibited angiotensin II-mediated aortic collagen remodeling and the resulting stiffening, analyzed with in vivo pulse wave velocity and effective Young’s modulus. Furthermore, the IL-2/ complex suppressed angiotensin II-mediated Th17 responses in the lymphoid organs and reduced gene expression of IL-17 as well as T cell and macrophage infiltrates in the aortic tissue. This study provides data that support the protective roles of Tregs in vascular stiffening and highlights the use of the IL-2/ complex as a new potential therapy in angiotensin II-related vascular diseases.