CD4+CD28null T cells in coronary artery disease: when helpers become killers

The crucial role of T cells in atherosclerosis and coronary artery disease (CAD) has been highlighted by recent observations. Helper CD4(+) T cells can both aggravate or attenuate the atherogenic process and the development of CAD. CD4(+)CD28(null) T cells are an unusual subset of helper cells which expand and have deleterious effects in CAD. In this review, we discuss the current issues on the generation of CD4(+)CD28(null) T cells and focus on their phenotypic and functional characteristics relevant to the development of cardiovascular events. The possible effects of the present day therapies for CAD on the CD4(+)CD28(null) T cells are also explored. Targeting the CD4(+)CD28(null) T cell subset in CAD could provide novel therapeutic strategies to prevent acute life-threatening coronary events.