Details

Autor(en) / Beteiligte

• 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

Titel

Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans

Ist Teil von

• Hypertension (Dallas, Tex. 1979), 2016-07, Vol.68 (1), p.123-132

Ort / Verlag

United States: American Heart Association, Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.