Heightened expression of survivin in activated T lymphocytes from patients with multiple sclerosis.
The perpetuation of the inflammatory process in multiple sclerosis (MS) may arise from the failure to eliminate potentially pathogenic autoreactive lymphocytes by programmed cell death (apoptosis). Such impairment may be caused by multiple abnormalities of apoptosis regulatory proteins. In this study, we investigated the expression of survivin, a recently described cell cycle-regulated antiapoptosis protein, in lymphocytes from patients with active relapsing-remitting MS and appropriate controls. Survivin reactivity was detected in intrathecal lymphocytes from some MS patients, but not in resting peripheral lymphocytes. However, mitogen stimulation of resting lymphocytes induced survivin expression, which was significantly higher in stimulated intrathecal and peripheral T lymphocytes from MS patients when compared to controls. In contrast, cellular expression of the antiapoptosis protein Bcl-2 was relatively similar between MS patients and the control groups. Moreover, heightened survivin expression in MS patients correlated with T lymphocyte resistance to apoptosis, and was independent of cellular expression of the death receptor Fas. These findings suggest that upregulation of the antiapoptotic protein survivin in mitogen-stimulated T lymphocytes is a feature of multiple sclerosis.
Sharief
M K
MK
Department of Neuroimmunology, Guy's, King's and St. Thomas' School of Medicine, Hodgkin Building, Guy's Hospital, SE1 9RT, London, UK. m.k.sharief@kcl.ac.uk
Semra
Y K
YK
D017209:Apoptosis / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008213:Lymphocyte Activation / Q000276:immunology; D008869:Microtubule-Associated Proteins; D008934:Mitogens / Q000494:pharmacology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins; D000077022:Survivin; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D008934:Mitogens; D009363:Neoplasm Proteins; D000077022:Survivin