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

Autor: Supannikar Tawinwung, Beenish A. Majeed, Nicolas Larmonier, Lance S. Eberson, Timothy W. Secomb, Douglas F. Larson
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: International Journal of Hypertension, Vol 2014 (2014)
International Journal of Hypertension
ISSN: 2090-0392
2090-0384
Popis: 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 lymphocytesin vivousing 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/mAbCD25concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val5]angiotensin II. Our results indicate that the IL-2/mAbCD25complex 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/mAbCD25complex inhibited angiotensin II-mediated aortic collagen remodeling and the resulting stiffening, analyzed within vivopulse wave velocity and effective Young’s modulus. Furthermore, the IL-2/mAbCD25complex 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/mAbCD25complex as a new potential therapy in angiotensin II-related vascular diseases.
Databáze: OpenAIRE
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