Activation of Human T Cells in Hypertension : studies of Humanized Mice and Hypertensive Humans
| Autor: | Daniel J. Moore, Wei Chen, William G. McMaster, Cornelia M. Weyand, Hana A. Itani, Rachel H. Bonami, Meena S. Madhur, Greg Poffenberger, David G. Harrison, Rafal R. Nazarewicz, Tomasz Mikolajczyk, Andrew F. Marshall, Andrzej Januszewicz, Mohamed A. Saleh, Anna M. Kaszuba, Anna Konior, Allison E. Norlander, Tomasz J. Guzik, Aleksander Prejbisz |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_specialty 030204 cardiovascular system & hematology Antibodies Monoclonal Humanized Kidney Lymphocyte Activation T-Lymphocytes Regulatory Sampling Studies Statistics Nonparametric Article 03 medical and health sciences Interleukin 21 Mice Random Allocation 0302 clinical medicine Immune system Reference Values Internal medicine Internal Medicine medicine Cytotoxic T cell Animals Humans Cells Cultured Interleukin 3 Analysis of Variance Chi-Square Distribution business.industry Angiotensin II Middle Aged Disease Models Animal 030104 developmental biology Endocrinology Humanized mouse Hypertension Interleukin 12 business CD8 |
| ISSN: | 0194-911X |
| Popis: | Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We used a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 versus 116 mm Hg for sham-treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta, and kidney revealed increased infiltration of human leukocytes (CD45 + ) and T lymphocytes (CD3 + and CD4 + ) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3 + /CD45RO + ) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T-cell proliferation. We also observed an increase in circulating interleukin-17A producing CD4 + T cells and both CD4 + and CD8 + T cells that produce interferon-γ in hypertensive compared with normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II. |
| Databáze: | OpenAIRE |
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