Natural killer (NK) cells and K cells mediating antibody-dependent cellular cytotoxicity have been shown to be large granular lymphocytes (LGL). The majority of LGL form lytic conjugates with a wide variety of NK-susceptible target cells. The relationship of soluble factors to this cell mediated lysis, has been examined using NK cytotoxic factors (NKCFs) as the mechanism of action. Three distinct steps have been defined for NKCF: a) production, b) binding to targets, and c) subsequent target lysis. With procedures able to independently measure these events, a variety of agents which have been reported to inhibit NK cell-mediated killing are being tested to determine their site of action. These NKCFs are produced by LGL and have a general specificity pattern similar to intact killer cells. Comparisons were made between NKCF and recombinant lymphotoxin (LT), tumor necrosis factor (TNF), and leukoregulin. The results demonstrated that NKCF is distinct from both these cloned factors. Studies are now in progress to purify NKCF using rat LGL cell lines as a source for secreted factor and ultimately for DNA/RNA when molecular cloning will be performed. In addition to lytic mechanisms, studies are presently underway to study the receptors and structures involved in NK recognition. Studies have been performed to determine the mechanism of cytotoxicity by mouse natural cytotoxic (NC) cells and to compare this information with the mechanism for cytotoxicity by natural killer (NK) cells. The NC-susceptible target cell, WEHI-164, has been found to be highly susceptible to both mouse and human recombinant tumor necrosis factor (rTNF) and antibodies to mouse TNF strongly inhibited NC activity. In contrast, the NK-susceptible target cell YAC-1 was resistant to lysis by TNF and anti-TNF did not affect NK activity.
