Angiotensin II Infusion Promotes Activation and Selective Cytokine Responses in Activated CD4 and CD8 T cells

Abstract

Hypertension affects roughly half of adults in the U.S. and is caused by several factors, including elevated angiotensin II (Ang II). T cells have been implicated in mechanisms of this pathology, however, data regarding T cell activation, including cytokine secretion and induction of activation markers are limited. This study investigated the hypothesis that Ang II increases T cell activation, as indicated by altered cytokine secretion and expression of surface markers associated with activation. To test this, 11-week-old C57Bl/6J male mice received saline vehicle or Ang II (490 ng/kg/min) via osmotic pump for 14 days (n=10/group) followed by immune cell isolation and ex vivo activation. Splenic T cells from Ang II-infused mice had modestly increased expression of CD25 (CD4: p=0.024, CD8: p=0.007), CD69 (CD4: p=0.017, CD8: p=0.032), and CD137 (CD8: p=0.022) 24 hours post-activation, as measured by median fluorescent intensity. The increased expression of activation markers correlated with an increase in select cytokines, including interleukin (IL)-28B (IFN{lambda}3) and interferon (IFN)-{gamma}-induced protein 10 (IP-10) at 24 hours and IFN{gamma} and IP-10 at 120 hours, while decreasing IL-23 at 120 hours. The increased expression of CD25 and CD69 suggests Ang II may increase the magnitude of T cell activation. This is further supported by the elevated induction of select cytokines all of which are associated with an antiviral response. Taken together, the data suggest Ang II modestly promotes T cell activation resulting in selective induction of cytokines associated with antiviral immunity.