Cooperation of natural killer cell stimulatory factor/interleukin-12 with other stimuli in the induction of cytokines and cytotoxic cell-associated molecules in human T and NK cells

Cell Immunol. 1994 Jul;156(2):480-92. doi: 10.1006/cimm.1994.1192.


The ability of natural killer cell stimulatory factor/interleukin-12 (IL-12) to induce cytokines other than IFN-gamma from both T and NK cells was studied. Both the direct effect of IL-12 and the cooperation between IL-12 and other cytokine inducers such as IL-2, phorbol diesters, and receptor antibodies were evaluated. It was found that IL-12 induces mRNA accumulation and production of GM-CSF and TNF-alpha from both T and NK cells and, as tested on NK cells only, induces M-CSF mRNA accumulation. Compared with cytokine inducers, IL-12 ability to induce IFN-gamma production was severalfold higher than its ability to induce GM-CSF or TNF-alpha. Likewise, the synergistic effect of IL-12 with the other stimuli to induce IFN-gamma was stronger than that observed in the case of GM-CSF or TNF-alpha. The IL-12-mediated enhancement of NK cytotoxicity is accompanied by an increased accumulation of mRNA for at least two genes encoding cytotoxic cell granule-associated proteins, the serine esterase granzyme B and the pore-forming protein perforin. IL-12 induction of perforin mRNA accumulation was not synergistic with either IL-2 or anti-CD16 stimulation, whereas granzyme B mRNA accumulation, induced by IL-2 or anti-CD16 stimulation, was slightly potentiated by IL-12. Thus, although IFN-gamma production is probably one of the most physiologically relevant effects of IL-12, induction of other cytokines by IL-12 in the presence of other inflammatory or immune stimuli may have a role in the in vivo functions of IL-12. The observation that both the IL-12-mediated enhancement of NK cell-mediated cytotoxicity and the increased expression of genes encoding cytotoxic cell granule-associated proteins were not cooperative with the effect of other NK cell activators suggests that the effect of IL-12 on cytotoxic cells is in part independent from that of other stimuli regulating the functions of these cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD3 Complex
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Cytotoxicity, Immunologic
  • Gene Expression / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • In Vitro Techniques
  • Interleukin-12
  • Interleukin-2 / pharmacology
  • Interleukins / pharmacology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, IgG
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics


  • CD3 Complex
  • Cytokines
  • Interleukin-2
  • Interleukins
  • RNA, Messenger
  • Receptors, IgG
  • Tumor Necrosis Factor-alpha
  • Interleukin-12
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Tetradecanoylphorbol Acetate