IL-18 AUGMENTS PERFORIN-DEPENDENT CYTOTOXICITY OF LIVER NK-T CELLS

The liver contains abundant cytotoxic cells, including NK-T cells, NK cells, and CTLs, However, the regulation of this cytotoxicity is not f ully understood. In this study, we investigated the effect of a recent ly described cytokine, IL-18, which is present in large quantities in the liver, on the cytotoxicity of intrahepatic lymphocyte subpopulatio ns, This effect of IL-18 was assessed by assaying the in vitro cytotox icity of purified NK-T, NK, and T cells against a CD95- and perforin-s ensitive T cell line, Jurkat. The results shaw that IL-18 enhances the killing activity of liver NK-T cells by a CD95-independent, perforin- dependent pathway. IL-18 also augments liver NK cell activity, but the exact mechanisms of this killing remain to be elucidated. Finally, th e augmentation of the killing activities of liver NK-T and NK cells by IL-18 is not due to soluble TNF-alpha, because none of these cell pop ulations had detectable TNF-alpha production.