Activation of human T cells in hypertension: studies of humanized mice and hypertensive humans

HA Itani, WG McMaster Jr, MA Saleh… - …, 2016 - Am Heart Assoc
HA Itani, WG McMaster Jr, MA Saleh, RR Nazarewicz, TP Mikolajczyk, AM Kaszuba…
Hypertension, 2016Am Heart Assoc
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 …
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.
Am Heart Assoc