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

Abstract EN

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 ( mAb CD25 ).

Three-month-old male C57BL/6J mice were treated with IL-2/ mAb CD25 concomitantly with continuous infusion of angiotensin type 1 receptor agonist, [Val5]angiotensin II.

Our results indicate that the IL-2/ mAb CD25 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/ mAb CD25 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/ mAb CD25 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/ mAb CD25 complex as a new potential therapy in angiotensin II-related vascular diseases.