The mechanism of activation of NK-cell IFN-γ production by ligation of CD28

Jason C. Cheung, Crystal Y. Koh, Brian E. Gordon, Julie A. Wilder, Dorothy Yuan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

We have investigated the mechanism by which anti-CD28 antibodies activates IFN-γ production by murine NK cells. These studies reveal that engagement of CD28 alone by this antibody is a poor activator of this cytokine response. Effective stimulation requires simultaneous ligation of the receptor for Fc (FcγRIII, CD16) which on its own is also a poor inducer of murine NK cells. The mechanism by which immobilized anti-CD28 increases IFN-γ mRNA abundance involves both upregulation of transcription as well as induction of mRNA stabilization. However, the elevation of transcription is not as evident as that induced by IL-12 which, in contrast, does not induce message stabilization. Thus ligation of CD28 in the presence of IL-12 results in a synergistic increase in production of the cytokine. Using this assay we have also determined that immobilized anti-CD28 cannot induce resting NK cells to produce IFN-γ. In contrast, the same cells can be induced by BCL1- C11 tumor cells that express high amounts of the CD28 ligand, B7-2. These studies provide important insights into the ability of cells bearing counter- receptor for CD28 to activate NK cell-cytokine production in vivo.

Original languageEnglish
Pages (from-to)361-372
Number of pages12
JournalMolecular Immunology
Volume36
Issue number6
DOIs
Publication statusPublished - Apr 1999

Keywords

  • CD28
  • FcγRIII
  • IFN-γ mRNA stability
  • IL-12
  • NK cells

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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