Regulatory T cells and the control of modified lipoprotein autoimmunity-driven atherosclerosis.

It has long been recognized that arterial inflammation plays a key role in the development of atherosclerosis. More recent evidence has suggested that this inflammation is modulated by autoimmune responses against modified self-antigens, such as oxidized low-density lipoprotein, in the vascular wall. However, the role of the immune system in atherosclerosis appears to be more complex than in classic autoimmune diseases; and a number of protective immune responses have also been identified. One of the most important of these is carried out by the regulatory T cells. Regulatory T cells inhibit the development of autoimmunity by controlling the activity of autoreactive T cells. If the function of regulatory T cells is compromised in hypercholesterolemic mouse models of atherosclerosis, the development of disease becomes much more aggressive. In this review, we will discuss the possibility that the inflammatory activity in atherosclerotic lesions depends on the balance between plaque antigen-specific proinflammatory Th1-type T cells and anti-inflammatory regulatory T cells specific for the same antigen. We will also discuss the role of hypercholesterolemia in generation of these modified self-antigens as well as ongoing research aiming to develop novel immune-modulating therapy for prevention of cardiovascular disease by targeting these processes. Copyright 2009 Elsevier Inc. All rights reserved.