Mahmoud Ahmad U M, Caillon Antoine, Shokoples Brandon, Ferreira Nathanne S, Comeau Kevin, Hatano Shinya, Yoshikai Yasunobu, Lewis Julia M, Tigelaar Robert E, Paradis Pierre, Schiffrin Ernesto L
Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research.
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
J Hypertens. 2025 Jan 1;43(1):109-119. doi: 10.1097/HJH.0000000000003871. Epub 2024 Sep 7.
γδ T cells mediate angiotensin II (AngII)-induced hypertension and vascular injury. γδ T cells expressing specific T-cell receptor (TCR) variable (V) γ chains develop in several waves in the thymus and migrate to specific or diverse tissues. We hypothesized that γδ T cells expressing specific Vγ subtypes in perivascular tissue mediate AngII hypertensive effects.
C57BL/6J male mice were infused or not with AngII (490 ng/kg/min, subcutaneously) for 14 days. γδ T-cell Vγ subtypes were profiled by flow cytometry in the spleen, descending thoracic aorta with adherent perivascular adipose tissue (DTAo/PVAT) and mesenteric vessels (MV)/PVAT. Other sets of AngII-infused mice were injected with control or specific anti-Vγ6 or Vγ4 antibodies. Blood pressure (BP) was determined by telemetry, and mesenteric artery function and remodeling by pressurized myography.
Vγ6/Vδ1 + γδ T cells represented more than 50% of the γδ T-cell Vγ subtypes in DTAo/PVAT and MV/PVAT, whereas Vγ1/2 + , Vγ4 + and Vγ6/Vδ1 + γδ T cells were the most abundant Vγ subtypes in the spleen. The frequency of Vγ6/Vδ1 + γδ T cells was increased at least 1.5-fold in the spleen and DTAo/PVAT, and tended to increase in MV/PVAT by AngII. A majority of Vγ6/Vδ1 + γδ T cells were activated in perivascular tissues. Vγ6/Vδ1 + γδ T-cell neutralization caused a steeper BP elevation and greater mesenteric artery endothelial dysfunction in mice infused with AngII. This was associated with more than three-fold increase in activated Vγ6/Vδ1 - γδ T cells in perivascular tissues. Depletion of Vγ4 + γδ T cells did not alter AngII detrimental effects.
Vγ6/Vδ1 + γδ T cells reduce the BP elevation and endothelial dysfunction induced by AngII infusion.
γδ T细胞介导血管紧张素II（AngII）诱导的高血压和血管损伤。表达特异性T细胞受体（TCR）可变（V）γ链的γδ T细胞在胸腺中以多波形式发育，并迁移至特定或不同的组织。我们假设血管周围组织中表达特定Vγ亚型的γδ T细胞介导AngII的高血压效应。
对C57BL/6J雄性小鼠皮下输注或不输注AngII（490 ng/kg/min），持续14天。通过流式细胞术分析脾脏、降胸主动脉及其附着的血管周围脂肪组织（DTAo/PVAT）和肠系膜血管（MV）/PVAT中γδ T细胞的Vγ亚型。给其他接受AngII输注的小鼠注射对照抗体或特异性抗Vγ6或Vγ4抗体。通过遥测法测定血压（BP），通过压力肌动描记法测定肠系膜动脉功能和重塑情况。
Vγ6/Vδ1 + γδ T细胞占DTAo/PVAT和MV/PVAT中γδ T细胞Vγ亚型的50%以上，而Vγ1/2 +、Vγ4 +和Vγ6/Vδ1 + γδ T细胞是脾脏中最丰富的Vγ亚型。AngII使脾脏和DTAo/PVAT中Vγ6/Vδ1 + γδ T细胞的频率至少增加1.5倍，MV/PVAT中的该频率有增加趋势。大多数Vγ6/Vδ1 + γδ T细胞在血管周围组织中被激活。Vγ6/Vδ1 + γδ T细胞的中和作用导致输注AngII的小鼠血压升高更陡，肠系膜动脉内皮功能障碍更严重。这与血管周围组织中活化的Vγ6/Vδ1 - γδ T细胞增加三倍以上有关。Vγ4 + γδ T细胞的耗竭并未改变AngII的有害作用。
Vγ6/Vδ1 + γδ T细胞可减轻AngII输注诱导的血压升高和内皮功能障碍。
