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Atherosclerosis is an immunoinflammatory disease elicited by accumulation of lipids in the artery wall and leads to myocardial infarction and stroke^,. Here, we show that naturally arising CD4⁺CD25⁺ regulatory T cells, which actively maintain immunological tolerance to self and nonself antigens^,, are powerful inhibitors of atherosclerosis in several mouse models. These results provide new insights into the immunopathogenesis of atherosclerosis and could lead to new therapeutic approaches that involve immune modulation using regulatory T cells.