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.