S-40-3: MEMORY GAMMA DELTA T CELLS PLAY A ROLE IN HYPERTENSION

Abstract

Objectives: A subset of T cells, γδ T cells, participate in the pathogenesis of hypertension. It has been shown that memory T cells develop after a hypertensive insult and sensitize mice to develop hypertension to subsequent mild hypertensive stimuli. However, whether memory γδ T cells develop and play a role in hypertension is unknown. We hypothesize that memory γδ T cells form after a hypertensive challenge, and that they sensitize mice to develop hypertension to mild hypertensive stimuli. Methods: Ten-12-week-old C57BL/6J mice were exposed or not to a pressor dose of angiotensin II (490 ng/kg/min, SC) for two weeks, followed by a two-week washout period, and then infused with a subpressor dose of angiotensin II (140 ng/kg/min, SC) for two weeks. Blood pressure (BP) was measured by telemetry and memory γδ T cells profiled by flow cytometry. A subset of mice was injected IP with 400 μg of anti-T cell receptor γδ-depleting or isotype control antibodies 1 day before and 6 days after the initiation of second hypertensive challenge. A final subset was injected IV with 2.5x105 γδ T cells isolated from hypertensive or normotensive mice, and then exposed to a subpressor dose of angiotensin II as above. Results: Repeated hypertensive challenges yielded a higher systolic BP than one mild hypertensive stimulus (154 ± 4 vs 120 ± 3 mm Hg, P < 0.01). Two-week pressor dose angiotensin II increased effector memory γδ T cells in mesenteric artery perivascular adipose tissue (1.25 ± 0.37% vs. 0.24 ± 0.12%, P < 0.05) and mesenteric lymph nodes (1.49 ± 0.03% vs 0.82 ± 0.15%, P < 0.05). γδ T cell depletion reduced systolic BP elevation from day 8 (135 ± 5 vs 150 ± 5 mm Hg, P < 0.05) to day 13 of the second hypertensive challenge (150 ± 5 vs 163 ± 2 mm Hg, P < 0.05). Adoptive transfer of γδ T cells isolated from hypertensive compared to normotensive mice caused a greater systolic BP elevation in response to a subpressor dose of angiotensin II (159 ± 3 vs 142 ± 6 mm Hg, P < 0.01). Conclusion: Memory γδ T cells develop after a hypertensive challenge and sensitize mice to mild hypertensive stimuli. Memory γδ T cells may represent a novel therapeutic target to treat hypertensive humans.