Objective:
Both innate (monocyte/macrophages) and adaptive immune cells (T lymphocytes) have been shown to play a role in the development of vascular injury in hypertension. Recently, we demonstrated that a small subset of “innate-like” T lymphocytes, expressing the γ/δ 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 and Results:
Fourteen to 15-week old male C57BL/6 wild-type (WT) mice were infused with Ang II (490 ng/kg/min, SC) for 3, 7 and 14 days (n=5-7) and spleen T cell profile was determined by flow cytometry. A correlation was demonstrated between the frequency (FREQ) and the number (#) of activated CD69
+
γδ T cells and CD4
+
CD69
+
T cells (FREQ: r=0.41,
P
<0.05 and #: r=0.58,
P
<0.001) and CD8
+
CD69
+
T cells (FREQ: r=0.36,
P
<0.05 and #: r=0.50,
P
<0.01). We also demonstrated a high correlation between the # of CD69
+
γδ T cells expressing CD27, a marker of interferon-γ expressing cells and a member of the T-T interaction molecules, with CD4
+
CD69
+
(r=0.88,
P
<0.001) and CD8
+
CD69
+
(r=0.81,
P
<0.01) T cells after 7 days of Ang II infusion.
Conclusion:
This study demonstrated an association between CD27
+
CD69
+
γδ T cells and activated T cells. These results suggest that γδ T cells drive activation of other T cells in Ang II-induced hypertension. Targeting γδ T cells may contribute to reduce inflammation in hypertension.