Induction of sensitivity to NK-mediated cytotoxicity by TNF-α treatment: possible role of ICAM-3 and CD44

Abstract

SR-91 is a natural killer (NK)-resistant leukemic cell line expressing a low level of ICAM-1. Pre-treatment of SR-91 cells with TNF-α or IFN-γ, increased both ICAM-1 (CD54) expression on SR-91 cells and binding to the human NK cell line NK-92. However, only TNF-α-treated SR-91 cells became sensitive to killing by NK-92 cells. The increased binding induced by both cytokines and the TNF-α-induced sensitivity of SR-91 cells to NK-92 cell killing were abrogated by anti-LFA-1 mAb as well as by a combination of antibodies against the three ligands of LFA-1 (CD11a/CD18), ICAM-1 (CD54), ICAM-2 (CD102) and ICAM-3 (CD50). This indicated that LFA-1 interaction with the three ICAMs on SR-91 cells is essential for effector–target cell binding (which is a prerequisite for subsequent target cell lysis), but is insufficient to render the SR-91 cells sensitive to killing by NK-92 cells. TNF-α, but not IFN-γ also induced the activation of LFA-1, CD44 and β1 integrins on SR-91 cells. Based on these observations we propose that the differential effect of TNF-α and IFN-γ could be related to the activation of certain adhesion molecules on the surface of SR-91 cells by TNF-α that, upon interaction with their counter-receptors on NK-92 cells, lead to the activation of the NK-92 cells.