IMMUNOLOGICAL CONTROL MECHANISMS IN PLAQUE-FORMATION

Atherosclerosis is characterized by cholesterol accumulation, inflamma tion, and fibrous tissue formation. We have analyzed inflammatory comp onents of atherosclerotic plaques and obtained evidence for T lymphocy te activation and cytokine secretion. A molecular genetical characteri zation 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 proge nitors and respond to different antigenic epitopes. The latter are not yet known, and it is also unclear to what extent the lymphocytic infi ltrate in plaques represent a local immune response. Vascular effects of cytokines produced by plaque macrophages and lymphocytes were studi ed in cell culture and animal experiments. It was found that the T cel l cytokine, interferon-gamma, inhibits cholesterol accumulation and fo am cell formation by down-regulating the scavenger receptor on macroph ages. It also inhibits smooth muscle proliferation in culture and the formation of arterial restenosis after angioplasty in experimental ani mals. Together, these studies emphasize the importance of vascular-imm une interactions in the pathogenesis of atherosclerosis.