Role of the adaptive immune system in hypertension

Abstract

Recent studies have shown that both innate and adaptive immunity contribute to hypertension. Inflammatory cells, including macrophages and T cells accumulate in the vessel wall, particularly in the perivascular fat, and in the kidney of hypertensive animals. Mice lacking lymphocytes are resistant to the development of hypertension, and adoptive transfer of T cells restores hypertensive responses to angiotensin II and DOCA-salt challenge. Immune modulating agents have variable, but often-beneficial effects in ameliorating end-organ damage and blood pressure elevation in experimental hypertension. The mechanisms by which hypertension stimulates an immune response remain unclear, but might involve the formation of neoantigens that activate adaptive immunity. Identification of these neoantigens and understanding how they form might prove useful in the prevention and treatment of this widespread and devastating disease.

Figure 1

Working hypothesis describing the role of adaptive immunity in hypertension. We propose that hypertensive stimuli, such as angiotensin II, salt and reactive oxygen species affect the CNS, the kidney and the vasculature. The effects of angiotensin II and salt have predominant roles centrally, increasing sympathetic outflow and indirectly affects the kidney and vasculature, leading to salt and water retention and vasoconstriction. This promotes mild hypertension to values of approximately 135 mmHg (pre-hypertension). This promotes formation of neo-antigens that are processed by antigen presenting cells and lead to T cell activation. Activated T cells infiltrate the vasculature and kidney, promoting endothelial dysfunction, further vasoconstriction and salt and water retention and ultimately severe hypertension.