Search

The activity of natural killer (NK) cells can be augmented by incubation with interferons, or with other compounds, such as staphylococcal protein A, which stimulate interferon production. In the experiments described here we compared the patterns of lytic activity of human lymphoid effector cells, before (NK-B) and after (NK-A) short-term activation. Target cells used were K562, Clone I (a partially NK-resistant K562 variant), and those that had been preincubated with neuraminidase or trypsin. The results obtained include the following: proteases, but not neuraminidase, decreased lysis by NK-B, but not by NK-A, of both K562 and Clone I in the standard Cr-release assay. In the single cell assay, trypsin minimally decreased conjugate formation and the fraction of bound cells that were killed by NK-B, but did not reverse the increased lytic efficiency of NK-A. In the cold-target competition assay, Clone I, which does not compete as well with K562 for NK-B, did so equally well for NK-A. Trypsinized targets, regardless of their equal sensitivity to lysis by NK-A, were not as active competitors for NK-A. We conclude that the most reasonable interpretation is that K562 cells bear surface structures which can induce release of lytic mediators from NK-A under conditions that are not sufficient to stimulate NK-B. Although it appears that NK-A may respond to a smaller number of the same target molecules recognized by NK-B, the process must be better defined at the molecular level to exclude the possibility that there are qualitative differences between the proposed recognition structures for these two states of NK activity.

By depletion of effector-target conjugates and cloning, a variant of the human leukemic line K562 that is partially resistant to lysis by natural killer (NK) cells when tested under conditions of culture and assay identical to that of the parent has been derived. Its karyotype shows markers similar to the original K562. The resistant phenotype remains stable after over 1 year of continuous passage and persists in multiple replicate subclones. However, it can be killed to a degree equal to the parent by antibody-activated complement, antibody-dependent cellular mechanisms, and by effector cells activated by staphylococcal protein A. These observations and experiments on cold target competition suggest that on its surface there is a significantly decreased, absent, or blocked effective target structure for a major population of unstimulated peripheral blood NK cells.