Resistance to glucocorticoid-induced apoptosis in PLP peptide-specific T cell clones from patients with progressive MS.
Glucocorticoids (GC) are commonly used to treat inflammatory disorders such as multiple sclerosis (MS) and may exert their immunosuppressive activity by inducing apoptosis in activated lymphocytes. However, unlike relapsing-remitting MS patients, those with progressive disease respond poorly to GC treatment. The data in this communication indicate that PLP peptide-specific T cell clones from progressive, but not relapsing-remitting MS patients are resistant to GC-induced apoptosis in vitro, in a fashion associated with expression of B-7 co-stimulatory molecules. Thus, failure to respond to GC treatment may reflect defect in apoptosis that develop during the progressive stages of chronic inflammatory disease.
Correale
J
J
Department of Neurology, University of Southern California, School of Medicine, 1333 San Pablo Street, MCK 142, Los Angeles, CA 90033, USA. jcorreale@fleni.org.ar
Gilmore
W
W
Li
S
S
Walsh
J
J
Bassani
M M
MM
Lund
B
B
Arias
M
M
Weiner
L P
LP
D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D018797:Cell Cycle Proteins; D002999:Clone Cells; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000235:genetics; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins
D001324:Autoantigens; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D005938:Glucocorticoids; D007376:Interleukin-2; D008869:Microtubule-Associated Proteins; D018991:Myelin Proteolipid Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D003907:Dexamethasone