Modulation of leukemic cell sensitivity to lymphokine-activated killer cytolysis: role of intercellular adhesion molecule-1.

The role of CD11/CD18 leukocyte adhesion molecules and their ligands in mediating non-major histocompatibility complex (MHC) restricted lymphocyte cytotoxicity is controversial. In order to examine the role of target cell intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of lymphocyte function-associated antigen (LFA-1) (CD11a/CD18), we exposed the human leukemia cell line, HL-60, to a variety of agents implicated in modulating ICAM-1 expression and/or sensitivity to lymphocyte cytolysis. Exposure of HL-60 cells to retinoic acid (RA), interferon (IFN)-alpha, IFN-beta, and IFN-gamma induced protection from lymphokine-activated killer (LAK) cytolysis. Only RA and IFN-gamma induced ICAM-1 expression. Tumor necrosis factor and vitamin D3, which also induced ICAM-1 expression, increased HL-60 sensitivity to LAK lysis. Granulocyte-macrophage colony-stimulating factor also increased sensitivity to LAK lysis; ICAM-1 was not induced. The state of cellular differentiation and expression of class I and II MHC antigens also did not correlate with sensitivity to LAK cytolysis. Exposure of untreated HL-60 cells and HL-60 cells expressing ICAM-1 to monoclonal antibody (mAb) versus ICAM-1 did not modulate LAK sensitivity. Exposure of LAK cells to mAb versus LFA-1 partially inhibited cytolysis; mAb versus CD18 inhibited cytolysis more completely. HL-60 cells were resistant to natural killer lysis; exposure to the various experimental agents did not alter sensitivity. We conclude that leukemic cell sensitivity to LAK cytolysis can be modulated by a variety of agents. Although our results suggest a role for leukocyte CD11/CD18 adhesion molecules in LAK cytolysis, the poor correlation between ICAM-1 expression and sensitivity to LAK lysis suggest that interactions other than LFA-1/ICAM-1 conjugation may be more central to the processes involved.