Splenocytes cultured in low concentrations of IL-2 generate NK cell specificities toward syngenic and allogenic targets

Splenocytes cultured in the presence of 30-60 units/ml IL-2 for 5 days deve lop natural killer activity toward syngeneic and allogeneic tumor cell targ ets. The IL-2 activated splenocytes, themselves, are partially resistant, w hereas concanavalin A-activated T blast cells are completely resistant to k illing. Surprisingly, major histocompatibility complex (MHC)-I-negative tar get cells are also resistant to natural killer (NK)-cell-mediated killing. Cells resistant to killing were unable to block NK-cell-mediated killing of sensitive targets as judged from cold target cell inhibition experiments, and one type of target cells sensitive to killing did generally not cross-b lock killing of other killing-sensitive target cell types. Alloantigen expo sure of splenocytes, i.e., one-way mixed lymphocyte cultures, partially pre vents the development of NK-cell activity. Our data suggest that target str uctures which trigger killing activity of NK cells are determined by the ph enotype of the target cell and are dependent on its MHC class I expression disregarding the haplotype of the cell. (C) 2000 Academic Press.