Mechanisms of disease: the evolving role of regulatory T cells in atherosclerosis.

Atherosclerosis and related complications still represent the major cause of morbidity and mortality in the western world. The mechanisms that govern the progression and destabilization of atheromatous lesions are multiple and complex. Despite their widespread use, lipid-lowering agents do not provide sufficient protection from future clinical cardiovascular-associated events. Interest in the role of immunity in atherosclerosis and support for this relationship has grown significantly over recent years. This paradigm, in which inflammation is an instrumental process in plaque development and rupture, is further supported by studies showing that immune subsets are operative in atherosclerosis. Regulatory T-cell subpopulations consist of lymphocytes--with several phenotypic markers--that share the ability to suppress, by various mechanisms, inflammatory responses. These regulatory T cells consist of subsets such as interleukin-10 secreting type I regulatory cells, type 3 effector T-helper cells that produce transforming growth factor-beta, as well as adaptive and natural CD4(+)CD25(+) regulatory T cells. In this Review, I focus on the direct and indirect evidence for the involvement of regulatory T cells in atherogenesis in experimental models and in humans. The growing knowledge of the role of regulatory T cells could result in the future development of novel therapeutic modalities to attenuate atherosclerosis and stabilize vulnerable plaques.