Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening
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 vascula...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | International Journal of Hypertension |
| Online Access: | http://dx.doi.org/10.1155/2014/126365 |
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| author | Beenish Majeed Supannikar Tawinwung Lance S. Eberson Timothy W. Secomb Nicolas Larmonier Douglas F. Larson |
| author_facet | Beenish Majeed Supannikar Tawinwung Lance S. Eberson Timothy W. Secomb Nicolas Larmonier Douglas F. Larson |
| author_sort | Beenish Majeed |
| collection | DOAJ |
| description | 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, [Val5]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. |
| format | Article |
| id | doaj-art-ce2d6e5d6e374bdeadb9d04f8e078d32 |
| institution | Kabale University |
| issn | 2090-0384 2090-0392 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Hypertension |
| spelling | doaj-art-ce2d6e5d6e374bdeadb9d04f8e078d322025-02-03T01:22:21ZengWileyInternational Journal of Hypertension2090-03842090-03922014-01-01201410.1155/2014/126365126365Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic StiffeningBeenish Majeed0Supannikar Tawinwung1Lance S. Eberson2Timothy W. Secomb3Nicolas Larmonier4Douglas F. Larson5Saver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USASaver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USASaver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USADepartment of Physiology, College of Medicine, The University of Arizona, Tucson, AZ 85724, USADepartment of Pediatrics, College of Medicine, The University of Arizona, Tucson, AZ 85724, USASaver Heart Center, College of Medicine, The University of Arizona, Tucson, AZ 85724, USAAdaptive 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, [Val5]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.http://dx.doi.org/10.1155/2014/126365 |
| spellingShingle | Beenish Majeed Supannikar Tawinwung Lance S. Eberson Timothy W. Secomb Nicolas Larmonier Douglas F. Larson Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening International Journal of Hypertension |
| title | Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening |
| title_full | Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening |
| title_fullStr | Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening |
| title_full_unstemmed | Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening |
| title_short | Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening |
| title_sort | interleukin 2 anti interleukin 2 immune complex expands regulatory t cells and reduces angiotensin ii induced aortic stiffening |
| url | http://dx.doi.org/10.1155/2014/126365 |
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