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 language | English |
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Pages (from-to) | 361-372 |
Number of pages | 12 |
Journal | Molecular Immunology |
Volume | 36 |
Issue number | 6 |
DOIs | |
Publication status | Published - Apr 1999 |
Externally published | Yes |
Keywords
- CD28
- FcγRIII
- IFN-γ mRNA stability
- IL-12
- NK cells
ASJC Scopus subject areas
- Immunology
- Molecular Biology