David G. Harrison, M.D. , F.A.C.C., F.A.H.A

Our laboratory has been focused on understanding how inflammation, and in particular, the adaptive immune response contributes to hypertension. Several years ago, we found that T cells are essential for the development of hypertension. We have shown that various hypertensive stimuli, including angiotensin II, norepinephrine and DOCA-salt cause activation of T cells and leads to their accumulation in the perivascular fat and kidneys. Our data indicate that T cell-derived cytokines such as IL-17 and TNF-a enhance vasoconstriction and sodium retention, leading to the hypertensive phenotype. Central signals derived from the circumventricular organs contribute to T cell activation, and manipulation of signals from this region affect T cell activation and the eventual elevation in blood pressure caused by angiotensin II. We are attempting to understand mechanisms involved in T cell activation in response to hypertensive stimuli. We have recently shown that gamma-ketoaldehydes, or isoketals adduct to proteins in hypertensive mice and humans, and that these are immunogenic. These modified proteins seem to act as "auto-antigens" that promote dendritic cell and ultimately T cell activation in hypertension.