UC Irvine

These in vitro studies were conducted in an attempt to elucidate the mechanism of how cell-free supernatant fluids obtained from PHA-stimulated human lymphocytes cause destruction of cells. The undiluted supernatant fluids with high activity exerted a nonspecific cytotoxic effect on many different continuous cell lines. However, upon dilution, a wide spectrum of cell sensitivities was observed. These studies suggest human lymphotoxin acts by first absorbing to receptors on the target cell plasma membrane. The next effect is shut-down of cellular DNA synthesis, followed later by a decrease in cell numbers and finally, cellular destruction. Once sufficient LT has bound to the target cell surface, the cytopathic effect is irreversible. A role for LT in lymphocyte-mediated tissue destruction is discussed.