Oligodendrocyte lysis by CD4+ T cells independent of tumor necrosis factor.
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.
Antel
J P
JP
Department of Neurology, McGill University, Montreal, Quebec, Canada.
Williams
K
K
Blain
M
M
McRea
E
E
McLaurin
J
J
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000276:immunology; D017628:Microglia / Q000276:immunology; D008934:Mitogens / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000502:physiology; D009836:Oligodendroglia / Q000276:immunology*; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha
D008934:Mitogens; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha