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2016 ; 118
(8
): 1233-43
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CD70 Exacerbates Blood Pressure Elevation and Renal Damage in Response to
Repeated Hypertensive Stimuli
#MMPMID26988069
Itani HA
; Xiao L
; Saleh MA
; Wu J
; Pilkinton MA
; Dale BL
; Barbaro NR
; Foss JD
; Kirabo A
; Montaniel KR
; Norlander AE
; Chen W
; Sato R
; Navar LG
; Mallal SA
; Madhur MS
; Bernstein KE
; Harrison DG
Circ Res
2016[Apr]; 118
(8
): 1233-43
PMID26988069
show ga
RATIONALE: Accumulating evidence supports a role of adaptive immunity and
particularly T cells in the pathogenesis of hypertension. Formation of memory T
cells, which requires the costimulatory molecule CD70 on antigen-presenting
cells, is a cardinal feature of adaptive immunity. OBJECTIVE: To test the
hypothesis that CD70 and immunologic memory contribute to the blood pressure
elevation and renal dysfunction mediated by repeated hypertensive challenges.
METHODS AND RESULTS: We imposed repeated hypertensive challenges using either
N(?)-nitro-L-arginine methyl ester hydrochloride (L-NAME)/high salt or repeated
angiotensin II stimulation in mice. During these challenges effector memory T
cells (T(EM)) accumulated in the kidney and bone marrow. In the L-NAME/high-salt
model, memory T cells of the kidney were predominant sources of interferon-? and
interleukin-17A, known to contribute to hypertension. L-NAME/high salt increased
macrophage and dendritic cell surface expression of CD70 by 3- to 5-fold. Mice
lacking CD70 did not accumulate T(EM) cells and did not develop hypertension to
either high salt or the second angiotensin II challenge and were protected
against renal damage. Bone marrow-residing T(EM) cells proliferated and
redistributed to the kidney in response to repeated salt feeding. Adoptively
transferred T(EM) cells from hypertensive mice homed to the bone marrow and
spleen and expanded on salt feeding of the recipient mice. CONCLUSIONS: Our
findings illustrate a previously undefined role of CD70 and long-lived T(EM)
cells in the development of blood pressure elevation and end-organ damage that
occur on delayed exposure to mild hypertensive stimuli. Interventions to prevent
repeated hypertensive surges could attenuate formation of hypertension-specific
T(EM) cells.