Defective post-thymic tolerance mechanisms during the chronic progressive stage of multiple sclerosis

Nat Med. 1996 Dec;2(12):1354-60. doi: 10.1038/nm1296-1354.

Abstract

We have recently isolated a panel of T-cell clones from chronic progressive multiple sclerosis (MS) patients that are capable of functioning as antigen-presenting cells and of expressing the costimulatory molecules B7-1 and B7-2. In this report we show that these T-cell clones are resistant to inhibitory regulation, including the induction of anergy and sensitivity to tumor growth factor-beta (TGF-beta)-induced growth inhibition. The resistance to anergy induction was associated with expression of B7 costimulatory molecules. These data suggest that lack of responsiveness to peripheral inhibitory signals may account for the entry of autoimmune diseases into a chronic progressive phase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal
  • Antigen-Presenting Cells / immunology
  • B7-1 Antigen / immunology
  • Cell Division / drug effects
  • Chronic Disease
  • Clonal Anergy*
  • Female
  • Histocompatibility Testing
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-2 / genetics
  • Interleukin-4 / biosynthesis
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Myelin Proteolipid Protein / immunology
  • RNA, Messenger / analysis
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / pharmacology

Substances

  • Antibodies, Monoclonal
  • B7-1 Antigen
  • Interleukin-2
  • Myelin Proteolipid Protein
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transforming Growth Factor beta
  • Interleukin-4
  • Interferon-gamma