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

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

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

Fingerprint

interleukin-12
natural killer cells
Interleukin-12
Natural Killer Cells
Chemical activation
cyclosporine
Cyclosporine
Messenger RNA
Transcription
Stabilization
transcription (genetics)
RNA Stability
Ligation
cytokines
Genes
Cytokines
antigens
Antigens
genes

ASJC Scopus subject areas

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

Cite this

Mechanism of induction of NK cell-IFN-γ production by anti-CD28 and IL-12. / Koh, C. Y.; Cheung, J. C.; Yuan, D.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

@article{80b4a0ba4b894250afcf5d6f567b397f,
title = "Mechanism of induction of NK cell-IFN-γ production by anti-CD28 and IL-12",
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.",
author = "Koh, {C. Y.} and Cheung, {J. C.} and D. Yuan",
year = "1998",
month = "3",
day = "20",
language = "English",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - Mechanism of induction of NK cell-IFN-γ production by anti-CD28 and IL-12

AU - Koh, C. Y.

AU - Cheung, J. C.

AU - Yuan, D.

PY - 1998/3/20

Y1 - 1998/3/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33749344105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749344105&partnerID=8YFLogxK

M3 - Article

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -