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Constitutive expression and role of the TNF family ligands in apoptotic killing of tumor cells by human NK cells.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1999 Nov 15; Vol. 163 (10), pp. 5358-66. - Publication Year :
- 1999
-
Abstract
- Natural killer cells mediate spontaneously secretory/necrotic killing against rare leukemia cell lines and a nonsecretory/apoptotic killing against a large variety of tumor cell lines. The molecules involved in nonsecretory/apoptotic killing are largely undefined. In the present study, freshly isolated, nonactivated, human NK cells were shown to express TNF, lymphotoxin (LT)-alpha, LT-beta, Fas ligand (L), CD27L, CD30L, OX40L, 4-1BBL, and TNF-related apoptosis-inducing ligand (TRAIL), but not CD40L or nerve growth factor. Complementary receptors were demonstrated to be expressed on the cell surface of solid tumor cell lines susceptible to apoptotic killing mediated by NK cells. Individually applied, antagonists of TNF, LT-alpha1beta2, or FasL fully inhibited NK cell-mediated apoptotic killing of tumor cells. On the other hand, recombinant TNF, LT-alpha1beta2, or FasL applied individually or as pairs were not cytotoxic. In contrast, a mixture of the three ligands mediated significant apoptosis in tumor cells. These findings demonstrate that human NK cells constitutively express several of the TNF family ligands and induce apoptosis in tumor cells by simultaneous engagement of at least three of these cytotoxic molecules.
- Subjects :
- Apoptosis Regulatory Proteins
CD27 Ligand
CD30 Ligand
Cytotoxicity Tests, Immunologic
Fas Ligand Protein
Gene Expression Regulation immunology
Humans
Killer Cells, Natural metabolism
Ligands
Lymphotoxin-alpha biosynthesis
Lymphotoxin-alpha genetics
Lymphotoxin-alpha metabolism
Lymphotoxin-beta
Membrane Glycoproteins biosynthesis
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
Membrane Proteins biosynthesis
Membrane Proteins genetics
Membrane Proteins metabolism
RNA, Messenger biosynthesis
Solubility
TNF-Related Apoptosis-Inducing Ligand
Transcription, Genetic immunology
Tumor Cells, Cultured immunology
Tumor Cells, Cultured metabolism
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Antigens, CD
Apoptosis immunology
Cytotoxicity, Immunologic
Killer Cells, Natural immunology
Tumor Necrosis Factor-alpha biosynthesis
Tumor Necrosis Factor-alpha physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 163
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 10553060