Oligodendrocyte lysis by CD4+ T cells independent of tumor necrosis factor

Ann Neurol. 1994 Mar;35(3):341-8. doi: 10.1002/ana.410350315.


The capacity of human CD4+ T cells to lyse heterologous human oligodendrocytes in an 18-hour chromium 51-release assay was compared to that of systemic blood-derived macrophages and central nervous system-derived microglia. CD4+ T cells, activated with either phytohemagglutinin, anti-CD3 antibody, or antigen (myelin basic protein), could induce lysis of the oligodendrocytes whereas macrophages and microglia, activated with interferon-gamma and lipopolysaccharide, could not. The CD4+ T-cell effect was not inhibited with an anti-tumor necrosis factor-alpha-neutralizing antibody. Both the CD4+ T cells and the macrophages could induce lysis of tumor necrosis factor-sensitive rodent cell lines, Wehi 164, and L929; these effects were inhibited with anti-tumor necrosis factor antibody. Pretreatment of the CD4+ T cells with cyclosporine or mitomycin C did not inhibit oligodendrocyte lysis. These results indicate that at least in vitro, CD4+ T cells can induce a form of oligodendrocyte injury that is not reproduced by macrophages or microglia or by tumor necrosis factor. The non-major histocompatibility complex (MHC)-restricted injury of oligodendrocytes induced by both myelin antigen-reactive and mitogen-stimulated T cells may provide a basis whereby cytotoxic CD4+ T cells could interact with a target cell that does not express MHC class II molecules. Our results suggest that immune-mediated oligodendrocyte/myelin injury, as is postulated to occur in the disease multiple sclerosis, may involve multiple effector mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytotoxicity, Immunologic / physiology*
  • Humans
  • In Vitro Techniques
  • Macrophages / immunology
  • Microglia / immunology
  • Mitogens / pharmacology
  • Myelin Basic Protein / physiology
  • Oligodendroglia / immunology*
  • Phenotype
  • Tumor Necrosis Factor-alpha


  • Mitogens
  • Myelin Basic Protein
  • Tumor Necrosis Factor-alpha