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Abstract The effects of different lymphocyte- and monocyte-derived mediators on human natural killer (NK) cell activity were examined. Human peripheral blood mononuclear cells (PBMC) or Percoll-enriched large granular lymphocytes (LGL) were preincubated in medium supplemented with lectin-free T cell growth factor (TCGF) preparations lacking interferon (IFN). Cells from these cultures exhibited a dose-dependent augmentation of NK cell activity against K562 leukemia cells, when compared with PBMC not incubated with TCGF. Furthermore, the addition of TCGF to PBMC or large granular lymphocytes in the presence of a maximally stimulatory concentration of human leukocyte interferon (IFN, 103 U/ml), resulted in levels of NK cell activity higher than that which either TCGF or IFN were capable of eliciting alone. Thus, it appears that TCGF is capable of directly stimulating human natural cell-mediated cytotoxicity. The effects of human leukocytic pyrogen/lymphocyte-activating factor (LP/LAF) on NK cell activity depended on the presence of other lymphokines during preincubation. Human NK cells preincubated in medium containing LP/LAF alone showed no augmentation of NK cell activity. However, when LP/LAF was added to PBMC in the presence of either TCGF or IFN, a marked synergistic augmentation of NK cell activity occurred. This augmentation produced by LP/LAF was dose dependent and maximal after 24 hr of incubation. The greatest augmentation of human NK activity was achieved with cells preincubated for 24 hr with LP/LAF, TCGF, and IFN. These studies demonstrate that human NK cell activity is subject to regulation by a variety of lymphokines and monokines. The possible mechanisms of the observed augmentation of NK activity produced by these substances and the potential in vivo relevance of the synergistic interaction of these important immunoregulatory molecules are discussed.
Dempsey et al. (Wed,) studied this question.