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The effect of interferon (IFN) on target cell susceptibility to human natural killer (NK) cells and monocytes was analyzed in direct cell-mediated and their cytotoxic factor-mediated cytotoxicity assays. Treatment of K562 cells with IFN resulted in a decrease in their sensitivity to lysis by nonadherent lymphocytes and Percoll-purified large granular lymphocytes (LGL) when tested in a 4-hour 51Cr release assay. In contrast, the treatment did not affect the target susceptibility to monocytes purified by adherence to autologous serum-coated plastic surfaces. In the target-binding assay with LGL or monocytes the number of conjugates was not altered after IFN treatment of K562. Lymphocytes and monocytes were induced to release soluble cytotoxic factors, termed "natural killer cytotoxic factors (NKCF) and monocyte cytotoxic factors (MCF)," respectively, when co-cultured with K562. Both NKCF and MCF lysed K562 in a 48-hour microcytotoxicity assay or in an 18-hour 51Cr release assay in the presence of dactinomycin. IFN-treated K562 reduced or completely lost their ability to stimulate the release of NKCF, whereas they triggered MCF secretion as effectively as did the untreated K562. When lymphocytes or monocytes were pretreated with IFN, they released NKCF or MCF with augmented lytic activity. In contrast to the sensitivity to NK cell-mediated lysis, IFN pretreatment of K562 induced no change in their susceptibility to NKCF and MCF. When IFN was added to NKCF and MCF assays, the cytotoxicity was enhanced. The addition of IFN to K562 that had been pretreated with NKCF or MCF and washed resulted in no increase in lysis. The capacity of K562 to absorb the lytic activity of NKCF and MCF was not altered by IFN. These results indicate that IFN treatment of target cells can be used to distinguish the two distinct types of blood mononuclear cells with natural cytotoxicity, NK cells and monocytes, and that each effector cell type is stimulated to release cytotoxic factors by the different target determinant after the initial effector-target cell binding.

A T-cell-enriched lymphocyte subset of samples from 15 tumor patients was tested for primary cytotoxicity against autologous tumor cell preparations and against 1-3 different allogeneic tumor cell preparations from biopsy material. Allogeneic cytotoxicity occurred in only 1 of 10 patients with autologous reactivity. The lymphocytes of 14 patients were cultured with autologous cells from biopsy material for 6 days. These lymphocytes killed autologous targets, but only 1 patient's lymphocytes were cytotoxic against 1 of the 4 allogeneic tumors tested. Cocultivation with allogeneic cells from biopsy specimens generated cytotoxicity toward the sensitizing allogeneic cells in 3 of 9 test combinations. In 2 of 3 instances the effectors were also active against the autologous tumor cells. Cytotoxicity in primary and secondary tests occurred thus only rarely against allogeneic targets. This indicated either the presence of individual tumor-related antigens on the cells from biopsy material or reflected the histocompatibility restriction of T-cell-mediated cytotoxicity.