title: Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening.
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 (mAbCD25). Three-month-old male C57BL/6J mice were treated with IL-2/mAbCD25 concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val(5)]angiotensin II. Our results indicate that the IL-2/mAbCD25 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/mAbCD25 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/mAbCD25 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/mAbCD25 complex as a new potential therapy in angiotensin II-related vascular diseases.
authors.affiliation: Saver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA ; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Beenish
authors.identifier: 0000-0003-2219-8735
authors.initials: B
authors.lastname: Majeed
authors.affiliation: Saver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA ; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Supannikar
authors.identifier: 0000-0002-7194-221X
authors.initials: S
authors.lastname: Tawinwung
authors.affiliation: Saver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Lance S
authors.initials: LS
authors.lastname: Eberson
authors.affiliation: Department of Physiology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Secomb
authors.affiliation: Department of Pediatrics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.affiliation: Saver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA ; Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA ; Department of Physiology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA ; Department of Surgery, College of Medicine, The University of Arizona, Tucson, AZ 85724, USA ; Arizona Health Sciences Center, Room 4402, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Larson