EXPERIMENTAL GRAFT ARTERIOSCLEROSIS .2. IMMUNOCYTOCHEMICAL ANALYSIS OF LESION DEVELOPMENT

The development of progressive graft arteriosclerosis causes the majority of late deaths occurring in cardiac transplant recipients. The pathogenesis of this process remains unclear. In order to characterize the cellular composition of lesions progressively, we employed a model of graft arteriosclerosis in the rat involving untreated heterotopic cardiac allografts transplanted across minor histocompatibility barriers. Immunocytochemical studies were performed on arterial lesions in allografts removed at 15, 45, 75, and 120 days post-transplantation, using monoclonal antibodies specific for smooth muscle cells (HHF35, CGA7), monocytes/macrophages (ED1), T cells (W313), and endothelial cells (anti-vWf). We found areas of coronary intimal thickening demonstrated marked cellular heterogeneity. The earliest lesions involved the adherence of monocytes and T cells to the coronary endothelial surface. At later time points, we noted marked subendothelial accumulations of macrophages and occasional T cells in areas of intimal thickening. In contrast, smooth muscle cells were the major cell type identified in intimal lesions in 120-day-old allografts. Intimal macrophages are frequently seen in spontaneous human arteriosclerotic lesions; our findings suggest that macrophages, perhaps interacting with T cells, play an important role in the pathogenesis of graft arteriosclerosis.