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 fully understood. In this study, we investigated the effect of a recently described cytokine, IL-18, which is present in large quantities in the liver, on the cytotoxicity of intrahepatic lymphocyte subpopulations. This effect of IL-18 was assessed by assaying the in vitro cytotoxicity of purified NK-T, NK, and T cells against a CD95- and perforin-sensitive T cell line, Jurkat. The results show 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, the 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 populations had detectable TNF-alpha production.
Dao
T
T
Immunobiology Section, Yale University School of Medicine, New Haven, CT 06520, USA.
Mehal
W Z
WZ
Crispe
I N
IN
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D016207:Cytokines / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007369:Interferon Inducers; D020382:Interleukin-18; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma