Development of hypertension in humans and in animal models is associated with endothelial dysfunction and vascular remodelling, and stiffening of large and small arteries, leading to stroke, to cardiac hypertrophy, and eventually to heart failure, and to chronic kidney disease. The pathophysiology of hypertension and associated cardiovascular disease is complex. Neuro-humoral factors such as the renin–angiotensin–aldosterone and endothelin systems, the sympathetic nervous system, genetic predisposition, environmental factors such as a high salt intake, and ageing, in combination or independently contribute to elevation of blood pressure (BP), and BP and/or the pro-hypertensive stimuli induce cardiovascular injury. It is now well appreciated that low-grade inflammation plays a role in the development and progression of hypertension and cardiovascular disease. 1–4 Adhesion molecules, chemokines and cytokines, and innate (monocytes/macrophages) and adaptive immune cell infiltration (T lymphocytes) are enhanced in cardiovascular tissues in hypertension. Genetic manipulation and adoptive immune cell transfer experiments have demonstrated that deficiency in monocytes/macrophages, T helper (Th) 1, and Th17 lymphocytes counteract BP elevation and vascular injury in hypertensive models. Innate immune cells play a role in the initiation and subsequent direction of the adaptive immune response, key mechanisms in hypertension, and vascular injury. T regulatory lymphocytes (Treg), a subset of T lymphocytes that exert immunosuppressive actions on Th1, Th2, and Th17, are decreased in hypertensive models. We and others have shown using genetic manipulation and adoptive transfer experiments that Treg have the potential to reduce the development of hypertension and vascular or cardiac injury. Recently, we demonstrated using loss-offunction approaches that a small subset of T lymphocytes expressing cd T cell receptors (TCRs) instead of conventional ab TCRs, which have innate-like features, are required for angiotensin II-induced BP elevation and endothelial dysfunction, and activation of T effector lymphocytes. 5 Thus, most cellular components of the immune system in one way or another modulate cardiovascular injury and BP elevation.

Attraction of immune cells to sites of injury in altered cardiovascular tissues is mediated by increased expression of chemokines. 6 Immune cells expressing appropriate G protein-coupled chemokine receptors follow the increasing gradient of chemokines to the injury site. 7 Forty-five chemokine ligands (L) and 15 chemokine receptors (R) have been identified and are divided into four subgroups based on the spacing of conserved cysteine residues: CC, CXC, C, and CX3C. The chemokine ligand–receptor pairings are complex, as most chemokines bind more than one receptor, and vice versa. The roles of a few chemokine ligands and receptors have been studied in hypertension and associated cardiovascular injury. 6 CCL2 [monocyte chemoattractant protein 1 (MCP1)] directs the attraction of neutrophils, monocytes, and T cells to inflammation sites via CCR2. In hypertension, CCL2 and CCR2 expression is increased in cardiovascular cells and in circulating monocytes, respectively. 6 Ccr2 knockout experiments have shown that CCR2 plays a role in the development of vascular remodelling and in kidney injury in hypertension, but not in BP elevation. 8–10 CCR2 binds not only CCL2 but also CCL7, CCL8, CCL12, and CCL13, whereas CCL7 and CCL13 bind to other chemokine receptors. 7 CCL5 [regulated on activation, normal T cell expressed and secreted (RANTES)] attracts monocytes and …