Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity (CMC). I. Release of cytotoxic factors specific for NK-sensitive target cells (NKCF) during co-culture of NK effector cells with NK target cells.

Abstract It was recently demonstrated that PHA-stimulated murine spleen cells will release soluble natural killer cytotoxic factors (NKCF) selective for NK target cells. The cytotoxic activity of NKCF directed against YAC-1 target cells can be detected by trypan blue uptake after an incubation period of 24 to 48 hr. The role of NKCF in NK cell-mediated cytotoxicity (CMC) reactions was investigated by determining whether the functional characteristics of NKCF conform with the known characteristics of NK activity as defined in the 51Cr-release assay. The following lines of evidence demonstrate that NKCF meet several criteria required to establish their possible role in the lytic mechanism of NK CMC. 1) NKCF are released by murine spleen cells during co-culture with NK-sensitive target cells over an incubation period of up to 48 hr. 2) The effector cell that releases NKCF is Thy-1.2 negative and asialo-GM1 positive. 3) Spleen cells from nude mice released high levels of NKCF, whereas mutant beige (bg/bg) mouse spleen cells release low levels. 4) NKCF lyse only NKA and NKB target cells (YAC-1, RL♂1, FLD-3, and WEHI-164) and not NK-resistant target cells (P815, EL4, AKSL2, R1.1, Molt-4, K562, and Raji). 5) The NK-sensitive YAC-1 ceils adsorb NKCF more effectively than the NK-resistant EL4 or AKSL2 cell lines. Taking available data of the NK CMC system and the characteristics of NKCF into consideration, a model is proposed for NK CMC reactions in which NKCF play an integral role in the lytic step. In this model, the effector cell must be able to recognize the NK-sensitive target and then release NKCF. On the other hand, for lysis to be achieved, the NK target cell must be able to activate the NK effector cell, to adsorb NKCF, and to be lysed by NKCF.