Abstract 126: Role of V γ6 + γδ T Cells in Angiotensin Il-Induced Hypertension and Vascular Injury

Introduction: Both innate and adaptive immune cells (such as T lymphocytes) have been shown to play a role in hypertension and vascular injury. Recently, we demonstrated that a small subpopulation of T cells considered "innate-like", expressing the γδ T-cell receptor (TCR) rather than the much more frequent αβ TCR, plays a key role in hypertension and vascular injury. The number and activation of γδ T cells were increased after 7 days of angiotensin (Ang) II infusion, and absence of γδ T cells prevented the development of hypertension, endothelial dysfunction of resistance arteries, and activation of CD4 + and CD8 + T cells in mice infused with Ang II for 14 days. γδ T cells can be subdivided according to the TCR variant (V) subtype that is generally specific for a tissue. A subpopulation of γδ T cells in the lungs and skin 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 γδ T cells involved in hypertension are Vγ6 + . Methods: 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), and γδ T cell Vγ subtypes were profiled by flow cytometry in the spleen, mesenteric lymph nodes (MLNs), thoracic aortic (TA), perivascular adipose tissue (PVAT) and mesenteric artery (MA) PVAT. Results: In spleen and MLNs the most abundant γδ T cell Vγ subtypes were Vγ1,2 + and Vγ4 + followed by Vγ6 + , Vγ5 + and Vγ7 + . In TA PVAT, the most abundant γδ T cell Vγ subtype was Vγ6 + followed by Vγ4 + , Vγ1,2 + , Vγ5 + and Vγ7 + . In MA PVAT, the most abundant γδ T cell Vγ subtype was Vγ6 + followed by Vγ4 + , Vγ7 + , Vγ5 + and Vγ1,2 + . Ang II infusion increased the frequency of Vγ6 + γδ T cells in the spleen (% of CD3 + T cells: 0.77±0.09 vs. 0.5±0.02, P P P =0.07). The Vγ6 + γδ T cell frequency in MLNs was unaffected by Ang II infusion. Conclusion: A differential distribution of γδ T cell Vγ subtypes was observed in lymphoid organs compared to PVAT. Vγ6 + γδ T cells may play a role in hypertension. Targeting Vγ6 + γδ T cells could be a therapeutic approach to reduce inflammation in hypertension.