T-cell Cholesterol Accumulation, Aging, and Atherosclerosis

Abstract

Purpose of Review: The majority of leukocytes in advanced human atherosclerotic plaques are T-cells. T-cell subsets exert pro- or anti-atherogenic effects largely via the cytokines they secrete. Tregulatory cells (Tregs) are anti-inflammatory, but may lose these properties during atherosclerosis, proposed to be downstream of cholesterol accumulation. Aged T-cells also accumulate cholesterol. The effects of T-cell cholesterol accumulation on T-cell fate and atherosclerosis are not uniform. Recent findings: T-cell cholesterol accumulation enhances differentiation into pro-atherogenic cytotoxic T-cells and boosts their killing capacity, depending on the localization and extent of cholesterol accumulation. Excessive cholesterol accumulation induces T-cell exhaustion or T-cell apoptosis, the latter decreasing atherosclerosis but impairing T-cell functionality in terms of killing capacity and proliferation. This may explain the compromised T-cell functionality in aged T-cells and T-cells from CVD patients. Summary: The extent of T-cell cholesterol accumulation and its cellular localization determine T-cell fate and downstream effects on atherosclerosis and T-cell functionality.