Abstract Body: Background: γδ T cells mediate angiotensin II (AngII)-induced blood pressure (BP) elevation, vascular injury and activated T cell infiltration in mesenteric vessels with adherent perivascular adipose tissue (MV/PVAT). γδ T cells expressing specific T cell receptor (TCR) variable (V) chain γ develop in several waves in the thymus and migrate to diverse tissues. We hypothesized that γδ T cells expressing specific Vγ subtypes in perivascular tissue are implicated in AngII detrimental hypertensive effects.

Methods: C57BL/6J male mice were infused or not with AngII (490 ng/kg/min, SC) for 14 days. Vγ1 and Vγ2 (Vγ1/2)⁺, Vγ4⁺, Vγ5⁺, Vγ6⁺, and Vγ7⁺ γδ T cell frequencies and T cell phenotypes were determined by flow cytometry in the spleen, descending thoracic aorta (DTAo)/PVAT, and MV/PVAT (n=7-13). Other sets of AngII-infused mice were injected with control or anti-Vγ6 (n=7-12) or Vγ4 antibodies (n=5-8). BP was determined by telemetry, mesenteric artery (MA) function and remodeling by pressurized myography, and T cell phenotypes by flow cytometry.

Results: In DTAo/PVAT and MV/PVAT, respectively, 43±5% and 51%±6% of γδ T cells were Vγ6⁺, and 17±2% and 23±4% Vγ4⁺, whereas in the spleen, 36±2% of the γδ T cells were Vγ1/2⁺, 32±1% Vγ4⁺ and 24±1% Vγ6⁺. AngII increased the frequency of Vγ6⁺ γδ T cells in the spleen (0.8±0.1 vs 0.5±0.0% of CD3, P<0.001) and DTAo/PVAT (5.9±0.8 vs 3.6±0.5% of CD3, P<0.05), and tended to increase their frequency in MV/PVAT. The majority of Vγ6⁺ γδ T cells were activated (CD69⁺) in DTAo/PVAT (75±5%) and MV/PVAT (84±2%). Vγ6⁺ γδ T cell depletion caused a steeper BP elevation (P<0.05) and worsened MA endothelial dysfunction (maximal acetylcholine relaxation response: 28±3 vs 55±8%, P<0.05) in mice infused with AngII. This was associated with increased CD69⁺ non-Vγ6⁺ γδ T cells in DTAo/PVAT (3.0±0.7 vs 0.8±0.4% of CD3, P<0.01) and MV/PVAT (15.2±2.6 vs 4.9±1.0% of CD3, P<0.01). Depletion of Vγ4⁺ γδ T cells in perivascular tissues, did not alter the AngII detrimental effects.

Conclusions: Vγ6⁺ γδ T cells are the most abundant γδ T cell Vγ subtype in perivascular tissues. AngII increased Vγ6⁺ γδ T cells in the spleen and perivascular tissue. Vγ6⁺ γδ T cell depletion in AngII-infused mice induced a steeper BP elevation, worsened MA endothelial dysfunction, and activated non-Vγ6⁺ γδ T cells. Vg6⁺ γδ T cells may play a protective role in AngII-induced hypertension and vascular injury.