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CALL FOR PAPERS
10th Annual Meeting for New Research in Cardiovascular and Kidney Diseases

Regulation of T-cell function by endogenously produced angiotensin II

¹Division of Cardiology, the Lowance Center of Human Immunology and the Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; and the ²Atlanta Veteran Administration Hospital, Decatur, Georgia

Submitted 19 June 2008 ; accepted in final form 1 November 2008

The adaptive immune response and, in particular, T cells have been shown to be important in the genesis of hypertension. In the present study, we sought to determine how the interplay between ANG II, NADPH oxidase, and reactive oxygen species modulates T cell activation and ultimately causes hypertension. We determined that T cells express angiotensinogen, the angiotensin I-converting enzyme, and renin and produce physiological levels of ANG II. AT₁ receptors were primarily expressed intracellularly, and endogenously produced ANG II increased T-cell activation, expression of tissue homing markers, and production of the cytokine TNF-. Inhibition of T-cell ACE reduced TNF- production, indicating endogenously produced ANG II has a regulatory role in this process. Studies with specific antagonists and T cells from AT₁R and AT₂R-deficient mice indicated that both receptor subtypes contribute to TNF- production. We found that superoxide was a critical mediator of T-cell TNF- production, as this was significantly inhibited by polyethylene glycol (PEG)-SOD, but not PEG-catalase. Thus, T cells contain an endogenous renin-angiotensin system that modulates T-cell function, NADPH oxidase activity, and production of superoxide that, in turn, modulates TNF- production. These findings contribute to our understanding of how ANG II and T cells enhance inflammation in cardiovascular disease.

cytokines; TNF-; electron spin resonance; adoptive transfer; NADPH oxidase; superoxide

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