T helper cell infiltration and foam cell proliferation are early events in the development of atherosclerosis in cholesterol-fed rabbits.
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 were 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Drew
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AF
Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Tipping
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PG
D000818:Animals; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D015704:CD4 Antigens / Q000276:immunology; D018956:CD5 Antigens / Q000276:immunology; D002455:Cell Division; D002465:Cell Movement; D002791:Cholesterol, Dietary; D005487:Foam Cells / Q000473:pathology*; D008297:Male; D011817:Rabbits; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology*
D015704:CD4 Antigens; D018956:CD5 Antigens; D002791:Cholesterol, Dietary