Regulation of APO-2 ligand/trail expression in NK cells-involvement in NK cell-mediated cytotoxicity

Cytokine. 1999 Sep;11(9):664-72. 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • 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
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics


  • Antibodies, Monoclonal
  • Apoptosis Regulatory Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-2
  • Membrane Glycoproteins
  • RNA, Messenger
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha