Immunological control mechanisms in plaque formation

Abstract

Atherosclerosis is characterized by cholesterol accumulation, inflammation, and fibrous tissue formation. We have analyzed inflammatory components of atherosclerotic plaques and obtained evidence for T lymphocyte activation and cytokine secretion. A molecular genetical characterization of T cell clones obtained from atherosclerotic lesions revealed that the cells are heterogeneous with regard to antigen receptor gene organization. This indicates that they are derived from several progenitors and respond to different antigenic epitopes. The latter are not yet known, and it is also unclear to what extent the lymphocytic infiltrate in plaques represent a local immune response. Vascular effects of cytokines produced by plaque macrophages and lymphocytes were studied in cell culture and animal experiments. It was found that the T cell cytokine, interferon-gamma, inhibits cholesterol accumulation and foam cell formation by down-regulating the scavenger receptor on macrophages. It also inhibits smooth muscle proliferation in culture and the formation of arterial restenosis after angioplasty in experimental animals. Together, these studies emphasize the importance of vascular-immune interactions in the pathogenesis of atherosclerosis.