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

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

Hypertension (Dallas, Tex. 1979), 2016-07, Vol.68 (1), p.123-132 [Periódico revisado por pares]

United States: American Heart Association, Inc

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Título:
Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans
Autor: 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
Assuntos: Adult ; Analysis of Variance ; Angiotensin II - pharmacology ; Animals ; Antibodies, Monoclonal, Humanized - immunology ; Cells, Cultured - drug effects ; Cells, Cultured - immunology ; Chi-Square Distribution ; Disease Models, Animal ; Humans ; Hypertension - drug therapy ; Hypertension - immunology ; Hypertension - physiopathology ; Kidney - drug effects ; Kidney - immunology ; Kidney - metabolism ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; Mice ; Middle Aged ; Random Allocation ; Reference Values ; Sampling Studies ; Statistics, Nonparametric ; T-Lymphocytes, Regulatory - drug effects ; T-Lymphocytes, Regulatory - immunology
É parte de: Hypertension (Dallas, Tex. 1979), 2016-07, Vol.68 (1), p.123-132
Notas: Drs. Itani and McMaster contributed equally to this work and should be considered co-first authors
Descrição: 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.
Editor: United States: American Heart Association, Inc
Idioma: Inglês

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

United States: American Heart Association, Inc

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