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

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Abstract
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‐γ and lipopolysaccharide, could not. The CD4+ T‐cell effect was not inhibited with an anti–tumor necrosis factor‐α–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.