Mechanism of induction of NK cell-IFN-γ production by anti-CD28 and IL-12

C. Y. Koh*, J. C. Cheung, D. Yuan

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

We have previously shown that the B lymphorna line, BCL1-C11, can directly activate NK cells in vitro as well as in vivo to produce IFN-γ. However, in vivo, full functional manifestation of this activation, ie isotype shift of an antigen-specific response, also requires IL-12. The activation of NK cells by BCL1-C11 can be partially blocked by CTLA4-Ig implicating a role for CD28 on NK cells. Therefore we have investigated the molecular basis for the activation of NK cells by anti-CD28 and compared it to activation by IL-12. We found that although IL-12 induces increased transcription of the IFN-γ gene the stability of the induced mRNA is not increased; therefore very little IFN-γ is produced. Stimulation by anti-CD28 induces, on the other hand, minimal effects on transcription but causes stabilization of the IFN-γ mRNA. Therefore a synergistic increase in mRNA accumulation is induced by anti-CD28 stimulation in the presence of IL-12. Interestingly, although activation by anti-CD28 is reduced by cyclosporine A (CsA), the induction of message stabilization is not affected. And, because stimulation by IL-12 is also CsA insensitive, the synergistic increase of IFN-γ mRNA production induced by the two stimuli is not abrogated by the addition of CsA. These studies provide the mechanistic basis for the interactive roles of IL-12 and ligation of relevant NK cell surface determinants in the induction of cytokine production in vivo.

Original languageEnglish
JournalFASEB Journal
Volume12
Issue number5
Publication statusPublished - Mar 20 1998

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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