Proatherogenic role for NK cells revealed.

Abstract

Atherosclerosis is now widely accepted as an inflammatory disease that involves both the innate and acquired immune systems.1 Several types of immune cells have been identified in the atherosclerotic lesions of humans and animal models. Numerous studies have shown a role for T and B lymphocytes in atherogenesis.2–6 Most studies have shown that T lymphocytes are proatherogenic, whereas B lymphocytes are associated with protection from atherosclerosis.2–6 The mechanisms for T and B lymphocyte–mediated modulation of atherosclerosis remain undefined, but may involve the production of proatherosclerotic cytokines, such as interferon (IFN)-γ, and the secretion of atheroprotective autoantibodies, respectively. See page 1049 Macrophages are particularly important to the atherosclerotic disease process. They are among the first cells to infiltrate the artery wall and regulate lesion growth from its inception through uptake of modified lipoproteins, production of apolipoprotein (apo)-E and regulation of cholesterol efflux, secretion of matrix metalloproteinases, and contribution to the inflammatory process.7,8 The importance of macrophages to atherosclerosis has been emphasized in animal models with defective macrophage biology such as the op/op and monocyte chemoattractant protein-1–deficient mice.9–11 In these cases, reduction in macrophage accumulation in the artery wall led to significant protection against atherosclerosis. Although the role of macrophages in atherosclerosis is now undisputed, the importance of other cells of the innate immune system has not yet been solidified. Few studies have looked at mast cells and neutrophils in atherosclerosis, and, until recently, not much had been determined regarding natural killer (NK) cells.1 NK cells are members of the innate immune system and are defined by their ability to lyse tumor cells in vivo.12 In addition, and perhaps more relevant to the atherogenic process, NK cells participate in innate immunity through the production of cytokines such as IFN-γ in response to interleukin (IL)-12 and …