Increased cellular expression of the caspase inhibitor FLIP in intrathecallymphocytes from patients with multiple sclerosis

Failure of Fas-mediated apoptosis of potentially pathogenic, autoreactive T lymphocytes may be involved in the pathogenesis of multiple sclerosis. The intracellular protein FLIP a naturally occurring caspase-antagonist, is a potent inhibitor of the Fas signalling pathway that may block Fas-mediated apoptosis of activated lymphocytes. This study reports specific overexpress ion of both long and short forms of FLIP in intrathecal lymphocytes from pa tients with multiple sclerosis. The overexpression of FLIP is independent o f cellular expressions of Fas receptor or the anti-apoptotic protein Bcl-2. These results provide a better understanding of some of the intrinsic immu noregulatory mechanisms that are involved in multiple sclerosis. (C) 2000 E lsevier Science B.V. All rights reserved.