A tumor necrosis factor-induced model of human primary demyelinating diseases develops in immunodeficient mice

We have reported previously that in the central nervous system (CNS) local expression of tumor necrosis factor (TNF) transgenes can trigger the develo pment of oligodendrocyte apoptosis, primary inflammatory demyelination and neurological dysfunction, accompanied by lymphocyte and macrophage infiltra tion into the CNS. To distinguish between the local effects of transgene-en coded TNF and the potential encephalitogenic effects of immune infiltrates upon CNS disease pathogenesis, we have backcrossed Tg6074 TNF-transgenic mi ce to mice deficient in CD4, beta 2-microglobulin (beta 2m), immunoglobulin mu chain (Ig mu) or recombination activation gene-1 (Rag-1). TNF was capab le of triggering undiminished primary demyelination in all of the immunodef icient mice, in the presence of activated cells of the macrophage/microglia l lineage. We conclude that TNF is sufficient to induce primary inflammator y demyelination and neurological deficits even in the absence of adaptive i mmunity.