Senescent T cells and hypertension: new ideas about old cells.

n textbooks of physiology and in medical school classrooms around the world, hypertension is described as a disease characterized by vascular dysfunction, renal impairment, and altered sympathetic outflow. T lymphocytes are never mentioned , and the notion that hypertension may be an autoim-mune disease is not even entertained. Yet, increasing evidence, dating back as early as the 1960s, supports a role of inflammation and immunity in the genesis of hypertension. Cells of both the innate and the adaptive immune systems infiltrate the vas-culature and kidney in various animal models of hypertension, and efforts to suppress inflammation reduce end organ damage and, in some instances, lower blood pressure. Mice and rats lacking T cells are partially protected against both angiotensin II and salt-sensitive hypertension, and adoptive transfer of T cells restores blood pressure in these animals. It is currently thought that cytokines released by inflammatory cells, including interleukin 17 (IL17), tumor necrosis factor-α, and IL6 lead to vascular dysfunction and remodeling and promote renal sodium retention, leading to blood pressure elevation. 1,2 Unfortunately, despite this growing body of evidence, almost all studies to date have been performed in experimental animals, and it is unclear whether adaptive immunity plays any role in human hypertension. Although there is considerable evidence in humans that inflammation is important in specialized cases, such as pulmonary hypertension 3 or pre-eclampsia (hypertension of pregnancy), 4 data that the immune system contributes to the pathophysiology of essential hypertension in nonpregnant adults are scarce. In 2005, Bautista et al 5 found a positive correlation between blood pressure and serum levels of tumor necrosis factor-α and IL6 in 196 relatively healthy subjects. IL6 functions both upstream and downstream of another highly proinflammatory cytokine, IL17, which is secreted from specialized subsets of T cells. We found that serum IL17 levels were positively correlated with blood pressure in 112 patients with diabetes mellitus. 6 In a small study of 8 patients with psoriasis or rheumatoid arthritis and grade 1 essential hypertension, treatment with the immunosuppressant drug, mycophenolate mofetil, reduced blood pressure and uri-nary excretion of tumor necrosis factor-α. 7 In this issue of Hypertension, Youn et al 8 provide interesting new data that suggest that T cells might indeed contribute to human hypertension. The authors used flow cytometry to demonstrate that hypertensive patients have an increased fraction of circulating CD8+ cytotoxic T cells bearing surface markers of immunosenescence. This phenotype is characterized by …