REGULATION OF FAS AND FAS-LIGAND EXPRESSION IN NK CELLS BY CYTOKINES AND THE INVOLVEMENT OF FAS-LIGAND IN NK/LAK CELL-MEDIATED CYTOTOXICITY

Abstract This study demonstrates cytokine-mediated regulation of Fas and Fas-ligand (Fas-L) expression in human NK cells and the involvement of the Fas-L pathway in NK/LAK cytotoxicity. Freshly isolated, highly purified human CD56 + CD3 − NK cells were found to express Fas and Fas-L. Cytokines further increased the Fas expression in the CD56 + CD3 − NK cells, with interleukin (IL)-2 being the most potent stimulus followed by IL-12, while IL-7 had no effect. IL-2 and ILK-7 equally enhanced the Fas expression in the CD56 + CD3 + population, while IL-12 had a less pronounced effect. Incubation of the CD56 + CD3 − NK cells with IL-2, but not with IL-12 and IL-7, led to an upregulation of the Fas-L expression, whereas neither of the cytokines affected the FAs-L expression in the CD56 + CD3 + cells. Antagonistic Fas mAb M3 and Fas–IgG1 fusion protein significantly inhibited NK cytotoxicity towards Fas-expressing Jurkat cells, while non-antagonistic Fas mAb M31 and irrelevant CD14-IgG1 fusion protein had no effect, Il-2-generated LAK cells were much more potent than NK cells in exerting the cytotoxic effect on Jurkat cells, which was also partially inhibited by M3 and Fas-IgG1. Thus, human NK and LAK cells express Fas and Fas-L, utilize the Fas-L cytotoxic pathway and enhance the expression of these molecules in response to cytokines.