Targeting T cell costimulation to prevent atherothrombosis.

Inflammation plays a key role in atherogenesis and precipitation of atherothrombosis. Immune cells, including macrophages and T cells, infiltrate the affected vascular wall, and inflammation drives build-up of atherosclerotic plaques.1–3 This concept of immune activation in atherosclerosis has become accepted, but specific therapy directed at inflammatory mechanisms is yet lacking.4 T cell activation regulated by costimulatory molecules plays an important role in experimental atherogenesis.5 Mounting evidence show that CD4 CD28 T cells have unique capabilities that potentially promote plaque vulnerability and atherothrombosis. In this issue of Circulation Research, Dimitriu et al identify alternative costimulatory molecules that regulate CD4 CD28 T cells and associate this mechanism with the process of plaque rupture.6