A dialysable acid factor from human leukocyte extracts activates tumor cell lysis mediated by human monocytes and natural killer cells.

Dialysable human leukocyte extract contains an acid natural killer (NK) cytotoxicity-stimulating factor, CySF-L1, which can be enriched by ion exchange chromatography. NK-cytotoxicity of human peripheral blood mononuclear cells (PBMC) against human K562 and HT29 tumor cells was strongly enhanced after 72 h pre-incubation with the factor. The CySF-L1-specific stimulation of PBMC required the presence of monocytes. The cytotoxic effector cells activated during preincubation of PBMC with CySF-1 were identified as monocytes and as NK cells present in the fraction of large granular lymphocytes (LGL). Selective cell depletion studies with LGL containing subpopulations (free of monocytes) indicated that the activated NK cells express CD 16 (Leu 11) and CD8 (T8) markers and the majority of them also the Leu7 marker. Analysis of the changes of surface marker expression of human PBMC during preincubation with CySF-L1 revealed an efficient stimulation of CD8 and TfR (transferrin receptor) expression, partly in conjunction with diminished expression of CD4 (T4). In vivo application of CySF-L1 after tumor challenge induced reduction of the incidence of tumor take and tumor development in mice.