Target cell DNA fragmentation is mediated by lymphotoxin and tumor necrosis factor

Supernatant fluids containing lymphotoxin (LT) activity were examined for their ability to mediate the fragmentation of cellular DNA in target L929 cells in the manner observed in cytotoxic T lymphocyte mediated killing. These supernatants were able to mediate L929 target cell DNA fragmentation, requiring a time course of 48 hours. In an effort to determine whether or not LT was directly involved in mediating this activity, recombinant-derived human lymphotoxin was tested for its ability to bring about the same effect. Both recombinant-derived LT and recombinant-derived tumor necrosis factor (TNF), a factor produced by macrophages and having some activities in common with LT, were able to cause DNA fragmentation in L929 over the same time course. Electrophoretic analysis of DNA isolated from LT-treated L929 target cells revealed that it is fragmented into low molecular weight fragments in a pattern similar to that produced in DNA isolated from target cells after attack by cytotoxic T cell lethal hit.