Activation of human t cells in hypertension: studies of humanized mice and hypertensive humans

Itani, H. A. et al. (2016) Activation of human t cells in hypertension: studies of humanized mice and hypertensive humans. Hypertension, 68(1), pp. 123-132. (doi: 10.1161/HYPERTENSIONAHA.116.07237) (PMID:27217403)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Guzik, Professor Tomasz
Authors: Itani, H. A., McMaster Jr, W. G., Saleh, M. A., Nazarewicz, R. R., Mikolajczyk, T. P., Kaszuba, A., Konior, A., Prejbisz, A., Januszewicz, A., Norlander, A. E., Chen, W., Bonami, R. H., Marshall, A. F., Poffenberger, G., Weyand, C. M., Madhur, M. S., Moore, D. J., Harrison, D. G., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
Publisher:American Heart Association
ISSN:0194-911X
ISSN (Online):1524-4563
Published Online:23 May 2016
Copyright Holders:Copyright © 2016 American Heart Association
First Published:First published in Hypertension 68(1):123-132
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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