Angiotensin II-Induced Memory γδ T Cells Sensitize Mice to a Mild Hypertensive Stimulus

Abstract

BACKGROUND: Memory T cells develop during an initial hypertensive episode, sensitizing mice to develop hypertension from further mild hypertensive challenges. We hypothesized that memory γδ T cells develop after a hypertensive challenge and sensitize mice to develop hypertension in response to a subsequent mild hypertensive challenge. METHODS: The first aim was to profile memory γδ T cells after a 14-day pressor dose angiotensin II (AngII) infusion (490 ng/kg/min, subcutaneously) in male mice. The second aim was to deplete γδ T cells during a second 14-day subpressor dose AngII challenge (140 ng/kg/min, subcutaneously) in mice pre-exposed to an initial pressor dose AngII challenge. The third aim was to transfer 2.5 × 105 live pre-activated or not γδ T cells from mice that had received a 14-day pressor dose AngII infusion or sham treatment, to naive recipient mice stimulated with a subpressor dose AngII infusion. RESULTS: Effector memory γδ T cells increased 5.2-fold in mesenteric vessels and perivascular adipose tissue, and 1.8-fold in mesenteric lymph nodes in pressor dose AngII-infused mice compared with sham-treated mice. Mice depleted of γδ T cells had 14 mm Hg lower systolic blood pressure (SBP) elevation than control mice from day 7 to 14 of subpressor dose AngII infusion. Adoptive transfer of γδ T cells from hypertensive mice induced an 18 mm Hg higher SBP elevation compared with a subpressor dose AngII infusion vs. γδ T cells transferred from sham-treated mice. CONCLUSIONS: Memory γδ T cells develop in response to hypertensive stimuli, and contribute to the pathogenesis of hypertension.