T cell subsets and functions in atherosclerosis

Atherosclerosis is a chronic inflammatory disease of the arterial wall and the primary underlying cause of cardiovascular disease. Data from in vivo imaging, cell-lineage tracing and knockout studies in mice, as well as clinical interventional studies and advanced mRNA sequencing techniques, have drawn attention to the role of T cells as critical drivers and modifiers of the pathogenesis of atherosclerosis. CD4(+) T cells are commonly found in atherosclerotic plaques. A large body of evidence indicates that T helper 1 (T(H)1) cells have pro-atherogenic roles and regulatory T (T-reg) cells have anti-atherogenic roles. However, T-reg cells can become pro-atherogenic. The roles in atherosclerosis of other T-H cell subsets such as T(H)2, T(H)9, T(H)17, T(H)22, follicular helper T cells and CD28(null) T cells, as well as other T cell subsets including CD8(+) T cells and gamma delta T cells, are less well understood. Moreover, some T cells seem to have both pro-atherogenic and anti-atherogenic functions. In this Review, we summarize the knowledge on T cell subsets, their functions in atherosclerosis and the process of T cell homing to atherosclerotic plaques. Much of our understanding of the roles of T cells in atherosclerosis is based on findings from experimental models. Translating these findings into human disease is challenging but much needed. T cells and their specific cytokines are attractive targets for developing new preventive and therapeutic approaches including potential T cell-related therapies for atherosclerosis. Accumulating evidence supports the critical role of T cells as drivers and modifiers of atherosclerosis. In this Review, Ley and colleagues describe the latest advances in our understanding of the role of T cell subsets in atherosclerosis, discuss the process of T cell homing to atherosclerotic plaques and highlight potential T cell-related therapies for atherosclerosis.