REGULATION OF APO-2 LIGAND/TRAIL EXPRESSION IN NK CELLS—INVOLVEMENT IN NK CELL-MEDIATED CYTOTOXICITY

• Published in: Cytokine (Philadelphia, Pa.) Vol. 11; no. 9; pp. 664 - 672
• Main Authors: Johnsen, Ann-Charlotte, Haux, Johan, Steinkjer, Bjørg, Nonstad, Unni, Egeberg, Kjartan, Sundan, Anders, Ashkenazi, Avi, Espevik, Terje
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.1999
• Subjects: Antibodies, Monoclonal - pharmacology; Apo-2 ligand/TRAIL/NK/cytotoxicity/apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Apoptosis - physiology; Apoptosis Regulatory Proteins; Cytotoxicity, Immunologic; Fas Ligand Protein; Gene Expression Regulation - drug effects; Humans; Immunophenotyping; Interleukin-2 - pharmacology; Jurkat Cells - drug effects; Jurkat Cells - pathology; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - pharmacology; Recombinant Proteins - pharmacology; RNA, Messenger - biosynthesis; TNF-Related Apoptosis-Inducing Ligand; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Apo-2 ligand/TRAIL/NK/cytotoxicity/apoptosis
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1999.0489

Apo-2L is a new member of the tumour necrosis factor (TNF) family shown to induce apoptosis in a number of tumour cell lines. Apo-2L mRNA is expressed by numerous human tissues. Here we report that Apo-2L is expressed and utilized by human Natural Killer (NK) cells. NK cells were shown to express surface Apo-2L in response to interleukin 2 (IL-2) activation, and this response was restricted to the CD3−population of the NK cells. Apo-2L mRNA and intracellular Apo-2L were present in both CD3−and CD3+NK cells; however, increased expression in response to IL-2 was only observed in CD3−CD56+cells. Also, IL-2-activated NK cells were shown to utilize membrane-bound Apo-2L in mediating lysis of Jurkat cells. Furthermore, Apo-2L-induced apoptosis of Jurkat cells was more rapid than FasL-induced apoptosis, indicating an important and distinct role for Apo-2L in apoptotic cell destruction. In conclusion, we report that NK cells express Apo-2L and that IL-2 activated CD3−NK cells utilize the Apo-2L pathway in mediating target cell lysis.