Dialysable factors from human leukocyte extracts activating human NK cytotoxicity against tumor cells: identification of factor-producing leukocyte subpopulations.

Dialysable human leukocyte extracts (10 kDa molecular weight cutoff) contain at least three cytotoxicity-stimulating factors CySF-L1, CySF-L2 and CySF-L3, activating natural killer (NK) cytotoxicity of human peripheral blood mononuclear cell (PBMC) against tumor cells when PBMC were pre-incubated with the factors for 72h prior to cytotoxicity assays. The factors could be separated by ion exchange chromatography on Dowex 50WX2. The leukocyte subpopulations producing these factors could be identified: CySF-L1 was detected in granulocyte extracts and T lymphocyte extracts, CySF-L2 in granulocyte extracts and monocyte extracts, CySF-L3 in T lymphocyte extracts and in B lymphocyte/NK cell extracts. All three factors were also present with low concentrations in fresh human plasma. The effector cells activated during pre-incubation of PBMC with the factors were partly identical: CySF-L1 and L2 activated the NK cytotoxicity of monocytes and of NK cells whereas CySF-L3 only stimulated the cytotoxicity of NK cells. All three factors stimulated LAK-like cytotoxicity since the effector cells showed enhanced activity not only against standard NK targets like K562 tumor cells but also against NK-insensitive targets like DAUDI cells and HT29 tumor cells.