IL-2 and NK LAK

Regulation of Fas and Fas-ligand expression in NK cells by cytokines and the involvement of Fas-ligand in NK/LAK cell-mediated cytotoxicity.

Medvedev AE, Johnsen AC, Haux J, Steinkjer B, Egeberg K, Lynch DH, Sundan A, Espevik T.

Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, Trondheim, Norway.

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, high 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 IL-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 at 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 to 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.

PMID: 9199873 [PubMed - indexed for MEDLINE]