Regulation of IFN-γ production in granulocyte-macrophage colony-stimulating factor-deficient mice Journal Article

Authors: Noguchi, Y.; Wada, H.; Marino, M. W.; Old, L. J.
Article Title: Regulation of IFN-γ production in granulocyte-macrophage colony-stimulating factor-deficient mice
Abstract: Granulocyte-macrophage colony-stimulating factor-deficient (GM-CSF-/-) mice produce far lower serum levels of IFN-γ in response to LPS than GM-CSF+/+ mice. CD4+ and CD8+ T cells from LPS-injected GM-CSF-/- mice showed a deficiency in IFN-γ production and proliferative activity in response to IL-2 and IL-12, whereas lFN-γ production by NK cells was not compromised. These defects of T cells were reversed by administration of GM-CSF in vivo, but not by supplementation with GM-CSF in vitro. GM-CSF-/- mice do not have an intrinsic defect in IFN-γ production, because IL-12 injection induces the same high levels of IFN-γ in GM-CSF-/- and GM-CSF+/+ mice. To investigate the inhibitory effect of LPS on GM-CSF-/- T cells and the indirect restorative activity of GM-CSF, we tested the action of supernatants from cultured dendritic cells (DC). A factor or factors in the DC supernatant normalized serum lFN-γ levels and T cell responses in LPS-injected GM-CSF-/- mice. IL-18 reproduced some but not all of these in vivo and in vitro effects of DC supernatants. Our results indicate that GM-CSF is important in protecting T cells from inhibitory signals generated during immunization or exposure to LPS, and that this effect of GM-CSF is indirect and mediated by factors produced by DC.
Keywords: controlled study; nonhuman; t lymphocyte; t-lymphocytes; animal cell; mouse; mouse mutant; animals; mice; mice, knockout; interleukin 2; dendritic cell; granulocyte macrophage colony stimulating factor; animal experiment; gene expression regulation; antigen presentation; gamma interferon; natural killer cell; lipopolysaccharide; cytokine production; interleukin 12; interleukin derivative; blood level; granulocyte-macrophage colony-stimulating factor; lipopolysaccharides; ifn-γ; interferon type ii; priority journal; article
Journal Title: European Journal of Immunology
Volume: 28
Issue: 12
ISSN: 0014-2980
Publisher: Wiley V C H Verlag Gmbh  
Date Published: 1998-12-01
Start Page: 3980
End Page: 3988
Language: English
PUBMED: 9862334
PROVIDER: scopus
DOI: 10.1002/(SICI)1521-4141(199812)28:12<3980::AID-IMMU3980>3.0.CO;2-D
Notes: Article -- Export Date: 12 December 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Lloyd J Old
    545 Old
  2. Michael W. Marino
    35 Marino