VARIANT GAMMA 6+ GAMMA-DELTA T CELLS PLAY A ROLE IN ANGIOTENSIN II-INDUCED HYPERTENSION

Abstract

Objective: We previously demonstrated that a small subpopulation of T cells considered (innate-like), expressing the γδ T-cell receptor (TCR) plays a key role in hypertension and vascular injury. γδ T cells can be subdivided according to the TCR variant (V) subtype that is generally specific for a tissue. A subpopulation of lungs and skin γδ T cells that are Vγ6+ and produce interleukin (IL)-17A was shown to respond promptly to pneumococcal infection and skin inflammation. However, γδ T cell Vγ subtypes involved in hypertension are still unknown. We hypothesized that the Vγ6+ γδ T cell may play a role in angiotensin (Ang) II-induced hypertension and vascular injury. Design and method: Eleven- to 13-week-old C57BL/6J male mice were infused or not with Ang II (490 ng/kg/min, SC) for 14 days, (n = 5–14). The γδ T cell Vγ subtypes were profiled and markers of activation of Vγ6+ γδ T cells were determined by flow cytometry. Results: In spleen and mesenteric lymph nodes (MLNs) the most abundant γδ T cells Vγ were Vγ1/2+ and Vγ4+ followed by Vγ6+,Vγ5+ and Vγ7+. In thoracic aortic (TA) perivascular adipose tissue (PVAT), the most abundant γδ T cell Vγ was Vγ6+ followed by Vγ4+, Vγ1/2+, Vγ5+ and Vγ7+. In mesenteric artery (MA) PVAT, the most abundant γδ T cell Vγ subtype was Vγ6+ followed by Vγ4+, Vγ7+, Vγ5+ and Vγ1/2+. Ang II increased the frequency of Vγ6+ γδ T cells in the spleen (1.5-fold, P < 0.01) and TA PVAT (1.6-fold, P < 0.01), whereas it only tended to increase them in MA PVAT. The frequency of IL-17 producing effector memory (CCR6 + CXCR3–CD44 + CD69 + ) Vγ6+ γδ T cells were increased in spleen (1.7-fold, P < 0.01) and trended to be elevated in mesenteric PVAT in Ang II-infused mice compared to control mice. Conclusions: Vγ6+ γδ T cells were the most abundant Vγ subtype in PVAT. IL-17 producing effector memory Vγ6+ γδ T cells may play a role in Ang II-induced hypertension. Targeting a γδ T cell variant subtype could be a therapeutic approach to reduce inflammation in hypertension.