Enhancement of T cell apoptosis correlates with increased serum levels of soluble Fas (CD95/Apo-I) in active lupus

Peripheral T cell apoptosis is upregulated in active SLE, in parallel with high expression of both membrane-bound and soluble (s) Fas. Previous studies postulated that sFas down-regulates apoptosis in vitro through its blockade of the Fas-L of cytotoxic cells. We have investigated the extent of apoptosis and sFas levels in 14 patients with active (group A) and 11 with inactive SLE (group B). Fas was predominantly expressed by CD3(+) cells from group A, whose increased serological levels of sFas were linearly correlated with the TUNEL positive cell population, whereas low titers paralleled a mild level of apoptosis in group B. This association was also investigated by measuring the effect of sFas on both cell proliferation and caspase activation. We found that incubation with sFas greatly suppressed proliferation of CD3(+) cells, especially in group B, and in control cells from healthy donors whose content of CPP32 active products was significantly increased. We postulate that sFas promotes a pro-apoptogen effect, which would explain the high susceptibility to apoptosis in active lupus, and that the apoptosis program itself includes release of sFas to spread the death signal.