Protective and pathogenic roles of CD8⁺ T cells in atherosclerosis

Although infiltration of CD8⁺ T cells in human atherosclerotic lesions has been described 30 years ago, the role of these cells in lesion development has long remained enigmatic. While experimental models hinted at their pro-atherogenic role based on circumstantial evidence, genetic mouse models of cytotoxic CD8⁺ T cell-specific immune deficiency suggested no crucial role of these cells in lesion development. However, in recent years, more refined models of adoptive cell transfer, disruption of specific immune regulatory pathways or monoclonal antibody-mediated cell depletion have proposed both atheroprotective and pro-atherogenic functions for CD8⁺ T cells in atherosclerosis. In particular, MHC class I-restricted CD8⁺ T cell responses may protect from atherosclerosis, and Qa-1 restricted regulatory CD8⁺ T cells have been defined. In addition, regulatory CD8⁺CD25⁺ T cells possess atheroprotective properties. However, CD8⁺ T cells can also promote monopoiesis in hyperlipidemia, and exert prototypical cytotoxic functions to promote vascular inflammation and macrophage accumulation leading to atherosclerotic lesion development. Here, we review these findings, mostly from experimental studies that reveal a previously unrecognized complexity and important role of CD8⁺ T cells in atherosclerosis.