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

被引:205
作者
Itani, Hana A. [1 ]
McMaster, William G., Jr. [1 ,2 ]
Saleh, Mohamed A. [1 ,6 ]
Nazarewicz, Rafal R. [7 ]
Mikolajczyk, Tomasz P. [8 ]
Kaszuba, Anna M. [8 ,9 ]
Konior, Anna [8 ]
Prejbisz, Aleksander [9 ]
Januszewicz, Andrzej [9 ]
Norlander, Allison E. [1 ]
Chen, Wei [1 ]
Bonami, Rachel H. [3 ]
Marshall, Andrew F. [4 ]
Poffenberger, Greg [5 ]
Weyand, Cornelia M. [7 ]
Madhur, Meena S. [1 ]
Moore, Daniel J. [4 ]
Harrison, David G. [1 ]
Guzik, Tomasz J. [8 ,10 ]
机构
[1] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Room 536 Robinson Res Bldg, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Gen Surg, Room 536 Robinson Res Bldg, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Dept Med, Div Rheumatol, Room 536 Robinson Res Bldg, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Div Endocrinol & Diabet, Dept Pediat, Room 536 Robinson Res Bldg, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Med Ctr, Dept Med, Div Endocrinol, Room 536 Robinson Res Bldg, Nashville, TN 37232 USA
[6] Mansoura Univ, Fac Pharm, Dept Pharmacol & Toxicol, Mansoura, Egypt
[7] Stanford Univ, Sch Med, Div Rheumatol & Immunol, Dept Med, Stanford, CA 94305 USA
[8] Jagiellonian Univ, Sch Med, Dept Internal & Agr Med, Krakow, Poland
[9] Inst Cardiol, Dept Hypertens, Warsaw, Poland
[10] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland
基金
英国惠康基金;
关键词
antigens; CD45; dendritic cells; inflammation; lymph nodes; myeloid cells; II-INDUCED HYPERTENSION; ATTENUATES HYPERTENSION; BLOOD-PRESSURE; INFLAMMATION; DISEASE; LYMPHOCYTES; INHIBITION; PSORIASIS; CD4;
D O I
10.1161/HYPERTENSIONAHA.116.07237
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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.
引用
收藏
页码:123 / +
页数:19
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