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

作者：Itani Hana A; McMaster William G Jr; 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

来源：Hypertension, 2016, 68(1): 123-+.

DOI：10.1161/HYPERTENSIONAHA.116.07237

• antigens, CD45
• dendritic cells
• inflammation
• lymph nodes
• myeloid cells

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-gamma 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.

• 出版日期2016-7