Blood pressure regulation by CD4(+) lymphocytes expressing choline acetyltransferase

Blood pressure regulation is known to be maintained by a neuro-endocrine circuit, but whether immune cells contribute to blood pressure homeostasis has not been defined. We previously described that CD4(+) T lymphocytes that express choline acetyltransferase (ChAT), which catalyzes the synthesis of the vasorelaxant acetylcholine, relay neural signals(1). Here we show that these CD4(+) CD44(high) CD62L(low) T helper cells by gene expression are a distinct T cell population defined by ChAT (CD4 T(ChAT)). Mice lacking ChAT expression in CD4(+) cells have elevated arterial blood pressure and echocardiographic assessment consistent with increased vascular resistance as compared to littermate controls. Jurkat T cells overexpressing ChAT (JT(ChAT)) decreased blood pressure when infused into mice. Co-incubation of JT(ChAT) increased endothelial cell levels of phosphorylated eNOS, and of nitrates and nitrites in conditioned media, indicating increased release of the potent vasodilator nitric oxide. The isolation and characterization of CD4 T(ChAT) cells will enable analysis of the role of these cells in hypotension and hypertension, and may suggest novel therapeutic strategies by targeting cell-mediated vasorelaxation.