Dual effect of glucocorticoids on apoptosis of human autoreactive and foreign antigen-specific T cells.
The efficacy of glucocorticoids in the treatment of multiple sclerosis may involve the induction of T cell apoptosis. Here, we report that glucocorticoids have two different effects on the vulnerability of human antigen-specific T cells: (i) steroids induce T cell apoptosis in a CD95-independent, but caspase-dependent manner; (ii) steroids protect T cells from CD95-mediated apoptosis which, however, is also caspase-dependent. An increase in BCL-2 expression is observed upon incubation with steroids. Thus, inhibition of CD95-mediated T cell apoptosis may be an undesirable side-effect resulting in survival of activated T cells and the maintenance of pathogenic immune responses might explain the lack of long-term glucocorticoid therapy.
Zipp
F
F
Department of Neurology, Division of Neuroimmunology, University Hospital Charité, Campus Mitte, NWFZ, Geb. 2680, R.04023, Schumann strasse 20-21, 10117, Berlin, Germany. frauke.zipp@charite.de
Wendling
U
U
Beyer
M
M
Grieger
U
U
Waiczies
S
S
Wagenknecht
B
B
Haas
J
J
Weller
M
M
D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000201:enzymology / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology; D053938:DNA Fragmentation / Q000276:immunology; D053222:Fas Ligand Protein; D005456:Fluorescent Dyes / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology; D008775:Methylprednisolone / Q000494:pharmacology*; D009103:Multiple Sclerosis / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D019014:fas Receptor / Q000235:genetics / Q000276:immunology
D001324:Autoantigens; D003374:Coumarins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D005456:Fluorescent Dyes; D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C102580:acetyl-aspartyl-glutamyl-valyl-aspartyl-amino-4-methylcoumarin; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D008775:Methylprednisolone