Resistance to glucocorticoid-induced apoptosis in PLP peptide-specific T cell clones from patients with progressive MS

J Neuroimmunol. 2000 Sep 22;109(2):197-210. doi: 10.1016/s0165-5728(00)00326-x.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • Autoantigens / immunology
  • Cell Cycle Proteins*
  • Clone Cells
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclins / genetics
  • Dexamethasone / pharmacology
  • Female
  • Gene Expression / immunology
  • Glucocorticoids / pharmacology
  • Humans
  • In Vitro Techniques
  • Interleukin-2 / genetics
  • Male
  • Microtubule-Associated Proteins / genetics
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / immunology*
  • Myelin Proteolipid Protein / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / analysis
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / immunology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins*

Substances

  • Autoantigens
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Glucocorticoids
  • Interleukin-2
  • Microtubule-Associated Proteins
  • Myelin Proteolipid Protein
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Dexamethasone