Comeau Kevin, Shokoples Brandon, Caillon Antoine, Paradis Pierre, Schiffrin Ernesto L
Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada.
Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Québec, Canada.
Am J Hypertens. 2023 Oct 13;36(11):619-628. doi: 10.1093/ajh/hpad072.
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.
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.
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.
Memory γδ T cells develop in response to hypertensive stimuli, and contribute to the pathogenesis of hypertension.
记忆性T细胞在初次高血压发作期间产生，使小鼠对进一步的轻度高血压刺激产生高血压敏感。我们假设记忆性γδT细胞在高血压刺激后产生，并使小鼠对随后的轻度高血压刺激产生高血压敏感。
第一个目的是在雄性小鼠中，在给予14天的升压剂量血管紧张素II（AngII）输注（490 ng/kg/分钟，皮下注射）后，分析记忆性γδT细胞。第二个目的是在预先接受初次升压剂量AngII刺激的小鼠中，在第二次14天的亚升压剂量AngII刺激（140 ng/kg/分钟，皮下注射）期间清除γδT细胞。第三个目的是将2.5×105个来自接受14天升压剂量AngII输注或假手术处理的小鼠的活的预激活或未预激活的γδT细胞，转移到接受亚升压剂量AngII输注刺激的未致敏受体小鼠中。
与假手术处理的小鼠相比，接受升压剂量AngII输注的小鼠的肠系膜血管和血管周围脂肪组织中的效应记忆性γδT细胞增加了5.2倍，肠系膜淋巴结中增加了1.8倍。在亚升压剂量AngII输注的第7天至第14天，清除γδT细胞的小鼠的收缩压（SBP）升高比对照小鼠低14 mmHg。与接受亚升压剂量AngII输注相比，从高血压小鼠过继转移γδT细胞诱导的SBP升高比从假手术处理的小鼠转移的γδT细胞高18 mmHg。
记忆性γδT细胞在高血压刺激下产生，并参与高血压的发病机制。
