Abstract P283: Gamma Delta T Cells Drive CD4 + and CD8 + T Cell Activation in Hypertension

Abstract

Objective: Both innate (monocyte/macrophages) and adaptive immune cells (T lymphocytes) 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 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. Method: 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 of 8 to 9-week-old C57BL/6 male mice. 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 activation 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. These correlations decreased after 14-day Ang II. 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. In vitro , Ang II increased the fraction of CD69 + αβ T cells when αβ T cells were co-cultured with γδ T cells (% of αβ T cells: 19.9±2.9 vs. 16.4±2.6, P <0.001) but not when cultured alone (% of αβ T cells: 13.7±0.7 vs. 12.7±0.6). A correlation between the fraction of CD69 + γδ T cells and CD69 + αβ T cells was also observed (r 2 =0.69, P <0.001). Conclusion: 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.