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Hypertension. 2016 Jul;68(1):123-32. doi: 10.1161/HYPERTENSIONAHA.116.07237. Epub 2016 May 23.

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

Author information

1
From the Division of Clinical Pharmacology, Department of Medicine (H.A.I., W.G.M., M.A.S., A.E.N., W.C., M.S.M., D.G.H.), General Surgery (W.G.M.), Division of Rheumatology, Department of Medicine (R.H.B.), Division of Endocrinology and Diabetes, Department of Pediatrics (A.F.M., D.J.M.), Division of Endocrinology, Department of Medicine (G.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt (M.A.S.); Divison of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, CA (R.R.N., C.M.W.); Department of Internal and Agricultural Medicine, Jagiellonian University School of Medicine, Krakow, Poland (T.P.M., A.M.K., A.K., T.J.G.); Department of Hypertension, Institute of Cardiology, Warsaw, Poland (A.M.K., A.P., A.J.); and Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland (T.J.G.).
2
From the Division of Clinical Pharmacology, Department of Medicine (H.A.I., W.G.M., M.A.S., A.E.N., W.C., M.S.M., D.G.H.), General Surgery (W.G.M.), Division of Rheumatology, Department of Medicine (R.H.B.), Division of Endocrinology and Diabetes, Department of Pediatrics (A.F.M., D.J.M.), Division of Endocrinology, Department of Medicine (G.P.), Vanderbilt University Medical Center, Nashville, TN; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt (M.A.S.); Divison of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, CA (R.R.N., C.M.W.); Department of Internal and Agricultural Medicine, Jagiellonian University School of Medicine, Krakow, Poland (T.P.M., A.M.K., A.K., T.J.G.); Department of Hypertension, Institute of Cardiology, Warsaw, Poland (A.M.K., A.P., A.J.); and Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland (T.J.G.). david.g.harrison@vanderbilt.edu.

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.

KEYWORDS:

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

PMID:
27217403
PMCID:
PMC4900908
DOI:
10.1161/HYPERTENSIONAHA.116.07237
[Indexed for MEDLINE]
Free PMC Article

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