Vγ6/Vδ1+ γδ T cells protect from angiotensin II effects on blood pressure and endothelial function in mice.

Abstract

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.