Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Apoptosis / drug effects
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Apoptosis / immunology*
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Autoantigens / immunology
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Cell Cycle Proteins*
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Clone Cells
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclins / genetics
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Dexamethasone / pharmacology
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Female
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Gene Expression / immunology
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Glucocorticoids / pharmacology
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Humans
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In Vitro Techniques
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Interleukin-2 / genetics
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Male
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Microtubule-Associated Proteins / genetics
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Middle Aged
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Multiple Sclerosis, Chronic Progressive / immunology*
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Myelin Proteolipid Protein / immunology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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RNA, Messenger / analysis
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T-Lymphocytes / cytology*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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Transforming Growth Factor beta / immunology
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Proteins*
Substances
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Autoantigens
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Glucocorticoids
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Interleukin-2
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Microtubule-Associated Proteins
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Myelin Proteolipid Protein
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Transforming Growth Factor beta
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Cyclin-Dependent Kinase Inhibitor p27
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Dexamethasone