Angiotensin II infusion increased systolic pressure (162 vs 116 mm Hg) and promoted human T cell activation and infiltration into critical end-organ tissues in a humanized mouse model.
Are human T cells activated and do they invade end-organ tissues in response to hypertension?
Human T cells become activated and invade critical end-organ tissues in response to the hypertensive milieu in vivo, supporting an immune component in the genesis of hypertension.
Absolute Event Rate: 162% vs 116%
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.
Itani et al. (Tue,) conducted a other in Hypertension. Angiotensin II vs. Sham treatment was evaluated on Systolic pressure. Angiotensin II infusion increased systolic pressure (162 vs 116 mm Hg) and promoted human T cell activation and infiltration into critical end-organ tissues in a humanized mouse model.
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