Role of membrane-associated lymphotoxin (mLT) in the killing activity of lymphokine-activated killer (LAK) cells towards various tumour cell lines.

Abstract

Human lymphokine-activated killer (LAK) cells developed by an incubation of peripheral mononuclear cells with IL-2 express the membrane-associated lymphotoxin (LT)-related molecule (mLT). By a further cultivation of mLT expressing (mLT-positive) LAK cells for 24 h without IL-2, mLT disappears (mLT-negative LAK cells). Cytotoxicities of various tumour cell lines by either mLT-positive or -negative LAK cells were compared. Eight out of 12 tumour cell lines, less susceptible to mLT-negative LAK cells than mLT-positive LAK cells, were categorized as group A. Two tumour cells (K562 and Molt-4) had the same susceptibility to both kinds of LAK cells. The others (Daudi and Jurkat) had less susceptibilities only when they were assessed at E:T ratios of less than 5. The four tumour cell lines in the latter two cases, containing K562, Molt-4, Daudi and Jurkat cells, were categorized as group B. The cytotoxicities of group A tumour cells, but not group B tumour cells, by LAK cells were significantly suppressed by the presence of anti-LT antibody. Group A tumour cells had higher LT-binding ability (2.82-16.44 fmol/10(6) cells) than group B tumour cells (less than 1.46 fmol/10(6) cells). Both mLT-positive and -negative LAK cells had similar perforin activities and tumour cell-binding capacities. These results suggest that the mLT-mediated killing mechanism is involved in tumour cell killing by LAK cells. Further, various tumour cell lines can be classified into two large groups according to their susceptibilities to the mLT-mediated killing by LAK cells.