Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans. Issue 1 (July 2016)

• Record Type: Journal Article
• Authors: Itani, Hana A.; McMaster, William G.; Saleh, Mohamed A.; Nazarewicz, Rafal R.; Mikolajczyk, Tomasz P.; Kaszuba, Anna M.; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E.; Chen, Wei; Bonami, Rachel H.; Marshall, Andrew F.; Poffenberger, Greg; Weyand, Cornelia M.; Madhur, Meena S.; Moore, Daniel J.; Harrison, David G.; Guzik, Tomasz J.
• Is Part Of: Hypertension. Volume 68:Issue 1(2016:Jul.)
• Publication Date: 2016-07
• Subjects: antigens, CD45 -- dendritic cells -- inflammation -- lymph nodes -- myeloid cells; Hypertension -- Periodicals; Hypertension -- Treatment -- Periodicals; 616.132005
• DOI: 10.1161/HYPERTENSIONAHA.116.07237
• Languages: English
• ISSNs: 0194-911X

Abstract

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. Abstract : Supplemental Digital Content is available in the text.