ACTIVATED T-CELLS INDUCE UP-REGULATION OF FAS ANTIGEN IN CULTURED ENDOTHELIAL-CELLS

Recent evidence has shown that apoptotic cells are present in human at herosclerotic lesions. However, the molecular mechanism of the inducti on of apoptosis in atherosclerotic lesions is not clear. Since T cells are present in almost all stages of atherosclerosis, we examined whet her T cells can modulate the expression of Fas, a death signal, in end othelial cells (ECs), using a coculture system. Human umbilical vein E Cs were cultured alone or cocultured with human peripheral T cells act ivated with phorbol myristate acetate and ionomycin. Flow cytometric ( FACscan) analysis showed that Fas antigen was up-regulated in ECs when ECs were cocultured for 24h with activated T cells. However, Fas anti gen was not up-regulated in ECs cocultured with non-activated T cells. The up-regulation of Fas antigen induced by coculturing ECs with acti vated T cells was partially, but significantly, neutralized by antibod y against interferon-gamma (IFN-gamma). Actually, incubation with IFN- gamma induced a dose-dependent increase in the level of Fas antigen in ECs cultured alone. These findings indicate that activated T cells in duce up-regulation of Fas antigen in ECs. Thus, the Fas system induced by activated T cells could participate in the mechanism of EC injury in atherosclerotic lesions.