Upregulation of the inhibitor of apoptosis proteins in activated T lymphocytes from patients with multiple sclerosis.
The pathogenesis of multiple sclerosis (MS) may involve failure of programmed cell death (apoptosis) to eliminate potentially pathogenic, autoreactive T lymphocytes. This failure may be caused by multiple abnormalities of the cell death machinery. In this study, we investigated the expression of the inhibitors of apoptosis (IAP) proteins, cellular IAP-1, IAP-2, and X-linked IAP (XIAP), in T lymphocytes from patients with active relapsing-remitting MS and appropriate controls. The expression of IAP proteins was significantly higher in mitogen-stimulated intrathecal and peripheral T lymphocytes from MS patients when compared to corresponding expressions from inflammatory and non-inflammatory neurologic controls, and healthy individuals. IAP proteins were also expressed in resting (unstimulated) T lymphocytes predominantly from MS patients. The heightened expression of IAP proteins in MS patients correlated with T lymphocyte resistance to apoptosis, and was independent of cellular expression of the death receptor protein Fas. In contrast, cellular expression of the anti-apoptosis protein Bcl-2 was relatively similar between MS patients and the control groups. These findings suggest that over-expression of IAP proteins 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, Guy's Hospital, Hodgkin Building, SE1 9RT, England, London, UK. m.k.sharief@kcl.ac.uk
Semra
Y K
YK
D017209:Apoptosis / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008213:Lymphocyte Activation / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000473:pathology; D011506:Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051636:X-Linked Inhibitor of Apoptosis Protein; D019014:fas Receptor / Q000378:metabolism
D051034:Inhibitor of Apoptosis Proteins; D008934:Mitogens; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D019014:fas Receptor