Reference - Detail
|Author||Kayagaki N, Yamaguchi N, Nakayama M, Takeda K, Akiba H, Tsutsui H, Okamura H, Nakanishi K, Okumura K, Yagita H.|
|Title||Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells.|
TNF-related apoptosis-inducing ligand (TRAIL), a new member of TNF family, induces apoptotic cell death of various tumor cells. We recently showed that TRAIL mediates perforin- and Fas ligand (FasL)-independent cytotoxic activity of human CD4+ T cell clones. In the present study, we investigated the expression and function of TRAIL on murine lymphocytes by using newly generated anti-murine TRAIL mAbs. Although freshly isolated T, B, or NK cells did not express a detectable level of TRAIL on their surface, a remarkable level of TRAIL expression was induced preferentially on CD3- NK1.1+ NK cells after stimulation with IL-2 or IL-15. In contrast, TRAIL expression was not induced by IL-18, whereas it efficiently potentiated lymphokine-activated killer activity of NK cells. In addition to perforin inactivation and neutralization of FasL by anti-FasL mAb, neutralization of TRAIL by anti-TRAIL mAb was needed for the complete inhibition of IL-2- or IL-15-activated NK cell cytotoxicity against mouse fibrosarcoma L929 target cells, which were susceptible to both FasL and TRAIL. These results indicated preferential expression of TRAIL on IL-2- or IL-15-activated NK cells and its potential involvement in lymphokine-activated killer activity.
|MeSH||Animals Antibodies, Monoclonal / chemistry Antibodies, Monoclonal / metabolism Apoptosis / genetics Apoptosis / immunology* Apoptosis Regulatory Proteins Cell Line Cytotoxicity, Immunologic Humans Interleukin-15 / pharmacology Interleukin-2 / pharmacology Killer Cells, Natural / immunology* Killer Cells, Natural / metabolism* Ligands Lymphocyte Activation* / genetics Male Membrane Glycoproteins / biosynthesis* Membrane Glycoproteins / genetics Membrane Glycoproteins / immunology Membrane Glycoproteins / metabolism Mice Mice, Inbred C57BL Rats Rats, Inbred F344 Recombinant Proteins / biosynthesis Recombinant Proteins / chemistry Recombinant Proteins / immunology Recombinant Proteins / metabolism TNF-Related Apoptosis-Inducing Ligand Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha / biosynthesis* Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factor-alpha / immunology Tumor Necrosis Factor-alpha / metabolism|
|DNA material||hTRAIL/pMKITneo (RDB02934) mTRAIL/pMKITNeo (RDB02935).|