Abstract 023: γδ T Cells Mediate αβ T Cell Activation in Angiotensin II-Induced Hypertension

Abstract

Objectives: Both innate and adaptive immune cells have been shown to play a role in hypertension and vascular injury. Recently, we demonstrated that a small subset of “innate-like” T lymphocytes, expressing the γδ T cell receptor (TCR) rather than the αβ TCR, plays a key role in hypertension and vascular injury. We demonstrated an increased number and activation (CD69 + ) of αβ and γδ T cells during the development of hypertension caused by angiotensin (Ang) II infusion, and that deficiency in γδ T cells prevented Ang II-induced hypertension, resistance artery endothelial dysfunction and spleen T-cell activation in mice. We hypothesized that γδ T cells mediate activation of other T cells in hypertension. Methods: C57BL/6 male mice were infused with Ang II (490 ng/kg/min, SC) for 7 and 14 days (n=5-7). All mice were 14-15 week-old at the end of the study. Spleen T cell profile was determined by flow cytometry. γδ and αβ T cells were isolated using magnetic beads from peripheral lymph nodes and spleen from C57BL/6 male mice treated or not with Ang II for 14 days. αβ T cells were cultured alone or with γδ T cells (5:1) in presence of anti-CD3 antibodies plus or minus Ang II, and αβ T cell phenotype was evaluated by flow cytometry. Results: Close correlations were demonstrated between the number (#) of activated CD69 + γδ T cells and CD4 + CD69 + T cells (r 2 =0.74, P <0.01) and CD8 + CD69 + T cells (r 2 =0.64, P <0.01) after 7-day Ang II infusion. Correlations were also shown between the # of CD27 + CD69 + γδ T cells and CD4 + CD69 + T cells (r 2 =0.76, P <0.001) and CD8 + CD69 + T cells (r 2 =0.65, P <0.01) after 7-day Ang II infusion. In vitro , Ang II increased the fraction of CD69 + αβ T cells when αβ T cells were co-cultured with γδ T cells isolated from control mice (% of αβ T cells: 19.9±2.9 vs. 16.4±2.6, P <0.001) but not when cultured alone. The fractions of CD69 + (% of CD69 + αβ T cells: 35.7±2.7 vs. 18.9±1.5, P <0.001) and CCR6 + αβ T cells (% of CCR6 + αβ T cells: 27.6±2.4 vs. 19.2±3.5, P <0.05) were increased when αβ T cells were co-cultured with γδ T cells isolated from Ang II-infused compared to control mice. Conclusions: These results suggest that γδ T cells mediate activation of αβ T cells in Ang II-induced hypertension. Targeting γδ T cells may contribute to reduce the low-grade inflammation found in hypertension.