Impaired Fas-independent apoptosis of T lymphocytes in patients with multiple sclerosis.
The homeostasis of the immune system is maintained by apoptotic (programmed cell death) elimination of potentially pathogenic, autoreactive mononuclear cells. There is emerging evidence that apoptosis mediated by the cell death receptor Fas is impaired in activated lymphocytes from patients with multiple sclerosis (MS), but other forms of apoptosis have not yet been fully evaluated. To further explore the dynamics of programmed cell death in MS, spontaneous and induced apoptosis of both peripheral and intrathecal mononuclear cells was investigated in clinically active MS patients and appropriate controls. In the MS group, spontaneous apoptosis of unfractionated mononuclear cells was significantly reduced, and activated intrathecal and peripheral T cells were found to be predominantly resistant to Fas-independent apoptosis. These results indicate that in clinically active MS, the reduced susceptibility of mononuclear cells to apoptosis is partly due to impairment of Fas-independent apoptotic pathways.
Sharief
M K
MK
Department of Neurology, Guy's, King's and St. Thomas's, School of Medicine, Guy's Hospital, Hodgkin Building, SE1 9RT, London, UK. m.sharief@umds.ac.uk
D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D002490:Central Nervous System / Q000166:cytology / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D019014:fas Receptor / Q000097:blood / Q000276:immunology*
D019014:fas Receptor