First Author | Noguchi Y | Year | 1998 |
Journal | Eur J Immunol | Volume | 28 |
Issue | 12 | Pages | 3980-8 |
PubMed ID | 9862334 | Mgi Jnum | J:114198 |
Mgi Id | MGI:3688485 | Doi | 10.1002/(SICI)1521-4141(199812)28:12<3980::AID-IMMU3980>3.0.CO;2-D |
Citation | Noguchi Y, et al. (1998) Regulation of IFN-gamma production in granulocyte-macrophage colony-stimulating factor-deficient mice. Eur J Immunol 28(12):3980-8 |
abstractText | Granulocyte-macrophage colony-stimulating factor-deficient (GM-CSF-/-) mice produce far lower serum levels of IFN-gamma in response to LPS than GM-CSF+/+ mice. CD4+ and CD8+ T cells from LPS-injected GM-CSF-/- mice showed a deficiency in IFN-gamma production and proliferative activity in response to IL-2 and IL-12, whereas IFN-gamma 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-gamma production, because IL-12 injection induces the same high levels of IFN-gamma 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 IFN-gamma 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. |