Membrane-associated lymphotoxin-expressing lymphokine-activated killer cells up-regulate intercellular adhesion molecule-1 expression on target tumor cells in vitro.

Human lymphokine-activated killer (LAK) cells cultured with interleukin-2 express membrane-associated lymphotoxin (mLT) on the cell surface. mLT-lacking (mLT-) LAK cells, which are generated by culturing without IL-2 for 24 hr, fully retained natural killer (NK) and LAK activity. However, they partially lost their killing activity against various tumor cells when compared to mLT-expressing (mLT+) LAK cells. An anti-LT but not anti-tumor necrosis factor (TNF) antibody somewhat suppressed the killing activity of mLT+ LAK cells against these tumor cells. However, an anti-LT antibody did not alter NK or LAK activity of mLT+ LAK cells. Anti-CD18 (beta chain of LFA-1) and anti-CD54 (ICAM-1) monoclonal antibodies, by inhibiting LAK cell binding to targets, suppressed the killing activity of mLT+ LAK cells. During the process in the cytotoxic assay, mLT+ but not mLT- LAK cells up-regulated ICAM-1 expression on target tumor cells, the effect of which was marginally inhibited by anti-TNF and anti-IFN-gamma but not by anti-LT antibodies. The up-regulation of ICAM-1 expression elicited by LAK cells on target tumor cells was not simply caused by diffused soluble factors but required membrane contact of LAK and target cells. Paraformaldehyde-fixed mLT+ but not mLT- LAK cells up-regulated ICAM-1 expression on target cells. These findings indicate that mLT+ but not mLT- LAK cells up-regulate ICAM-1 expression on target tumor cells via undetermined membrane factor(s), and this effect appears to be at least partially responsible for the higher killing activity of mLT+ LAK cells than that of those lacking mLT in vitro.