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

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.