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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1563-1568.)
© 1995 American Heart Association, Inc.

Articles

T Helper Cell Infiltration and Foam Cell Proliferation Are Early Events in the Development of Atherosclerosis in Cholesterol-Fed Rabbits

A.F. Drew; P.G. Tipping

From the Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.

Correspondence to P.G. Tipping, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria 3168, Australia.

Abstract The involvement of T cells in the early cellular events in atherosclerosis was studied in rabbits fed a 1% cholesterol diet by use of specific monoclonal anti-rabbit CD5 and CD4 antibodies. T cells were not seen in the aortic intimas of rabbits not fed cholesterol but were seen in intimal lesions in cholesterol-fed rabbits. Accumulation of T cells in plaques occurred between 2 and 4 weeks after commencement of cholesterol feeding, and the greatest density of CD5-positive T cells was observed after 4 weeks (11.2±6.0 cells/mm² [mean±SEM]; P<.02 compared with normal control rabbits, P<.03 compared with 2-week plaques). Staining for CD4 indicated that the majority of these T cells were T helper cells (9.9±4.9 cells/mm²). At this time, plaques showed a dense cellular infiltrate of macrophages (3623±467 cells/mm²) and macrophage proliferation was evident (2.1±1.1% of total plaque cells). As the cross-sectional area of intimal lesions increased progressively in subsequent weeks, their cellularity declined (8 weeks, 2239±271 cells/mm²; 12 weeks, 1535±55 cells/mm²; 16 weeks, 1747±242 cells/mm², P<.05 for all groups compared with the 4-week group). The density of the T cell infiltrate (8 weeks, 6.7±3.0 cells/mm²; 12 weeks, 0.6±0.2 cells/mm²; 16 weeks, 1.0±0.4 cells/mm²) and the proliferative index of cells within plaques (8 weeks, 0.6±0.2%; 12 weeks, 0.8±0.3%; 16 weeks, 0.2±0.2%) also declined. Smooth muscle cell capping was observed in these later plaques without smooth muscle cell proliferation. These studies demonstrate that helper T cell infiltration into plaques is an early event in atherogenesis and is associated with local macrophage proliferation, suggesting a role for T cells in the initiation of atherosclerosis.

Key Words: T lymphocyte • atherosclerosis • CD4 • CD5 • macrophage

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