Laboratory studies of type 1 diabetes and other autoimmune diseases show that boosting levels of tumor necrosis factor (TNF) or its receptor activity selectively destroys autoreactive T cells, suggesting a possible cure for the diseases, investigators here reported. CD4 cells and other populations of autoreactive CD8 cells proved invulnerable to TNF- or agonist-induced death. "With chronic diseases such as diabetes and other forms of autoimmunity, most therapies have traditionally used nonspecific immunosuppression, because it was thought that the rare autoreactive T cells could not be identified, much less selectively killed," the authors said.
"A defective NF signaling pathway, which leads to cell death, now provides, at least in vitro, a unique opportunity in human [autoimmune] diseases to kill only autoreactive T cells"
Noting that anti-TNF therapy has become a mainstay of treatment for rheumatoid arthritis and Crohn's disease, both autoimmune disorders, the authors said, "an expanding body of research in animal models . . . suggests the opposite strategy may be warranted."
Administration of TNF or a receptor agonist to isolated T-cells led to the death of a subpopulation of autoreactive CD8 cells to insulin, Denise Faustman, M.D., Ph.D., of Massachusetts General Hospital, and colleagues reported online in Proceedings of the National Academy of Sciences.
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