Abstract
Cytotoxic cytokine, human lymphotoxin (LT/TNF-s), is expressed on the membrane of human lymphokine-activated killer (LAK) cells of both natural killer and T cell origin. Human LAK cells express mLT and produce soluble LT. The levels of mLT expression were correlated with IL-2 concentration in culture media. mLT is lytically active, which is shown by paraformaldehyde fixation of LAK cells. Moreover, LAK cells without fixation showed cytotoxicity against L929 cells, which was partly neutralized by anti-LT but not anti-TNF antibody. mLT negative LAK cells, manipulated by 24 hours culture of mLT positive LAK cells using media without IL-2, partly lost the killing activity against several human tumor cell lines such as MIA PaCa human pancreatic cancer cell. Killing activity of mLT positive LAK cells against these tumor cell lines was partly neutralized by anti-LT but not anti-TNF antibody. Collectively, our data indicate that mLT is an important tumoricidal effector molecule expressed on LAK cells for adoptive immunotherapy.
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