Overexpression of the apoptosis inhibitor FLIP in T cells correlates with disease activity in multiple sclerosis.

The cellular caspase-inhibitory protein FLIP has been recently identified as a potent regulator of T lymphocyte susceptibility to Fas-mediated programmed cell death (apoptosis). Since impairment of apoptosis may be involved in multiple sclerosis (MS), we investigated the dynamics of cellular FLIP in unstimulated and activated T lymphocytes from MS patients, inflammatory and non-inflammatory neurological disorders, and healthy subjects. Cellular expression of the long and short forms of FLIP protein was similar in unstimulated T cells from MS patients and controls, but was significantly higher in activated T cells from patients with clinically active MS. This high FLIP expression in active MS correlated with cellular resistance to Fas-mediated apoptosis. In contrast, cellular expression of the anti-apoptotic protein Bcl-2 did not differ between active and stable disease, and was relatively similar between the MS group and controls. These findings suggest that cellular overexpression of the anti-apoptotic protein FLIP is a feature of clinically active multiple sclerosis.