Elevated Bcl-X(L) levels correlate with T cell survival in multiple sclerosis.
T cell resistance towards apoptotic elimination by activation-induced cell death (AICD) might be a crucial pathogenic feature of multiple sclerosis (MS). Since the Bcl-2 family is critically involved in the regulation of apoptosis, we investigated the protein expression of Bcl-2, Bcl-X(L), and Bax in peripheral blood mononuclear cells (PBMC) of 23 MS patients and 29 control subjects. An in vitro model of AICD, which exemplifies the elimination of antigen-reactive T cells in vivo, was used as an indication of T cell susceptibility or resistance towards apoptosis. Increased expression of the survival factor Bcl-X(L), which directly correlated with a resistance towards AICD, was observed in peripheral immune cells of MS patients. In contrast to Bcl-X(L), no differences were found in the protein expression of Bcl-2 and Bax between patients and controls. Our data indicate that the anti-apoptotic factor Bcl-X(L), responsible for T cell resistance towards apoptosis, might be an important factor in the MS pathogenesis and a potential target for therapeutic intervention.
Waiczies
Sonia
S
Division of Neuroimmunology, Department of Neurology, Neuroscience Research Center, Charité University Hospital, Building 2680, Schumannstr. 20/21, 10117 Berlin, Germany.
Weber
Alexandra
A
Lünemann
Jan D
JD
Aktas
Orhan
O
Zschenderlein
Rolf
R
Zipp
Frauke
F
D000328:Adult; D017209:Apoptosis / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology*; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein