Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survivalin vivo

European Journal of ImmunologyVolume 30, Issue 7 p. 1813-1822 ArticleFree Access Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo Manfred B. Lutz, Corresponding Author Manfred B. Lutz [email protected] Department of Dermatology, University of Erlangen, Erlangen, GermanyDepartment of Dermatology, University of Erlangen, Hartmannstr.14, D-91052 Erlangen, Germany Fax: +49–9131–853–6417Search for more papers by this authorRakesh M. Suri, Rakesh M. Suri Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, GBSearch for more papers by this authorMasanori Niimi, Masanori Niimi Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorAlexandra L.J. Ogilvie, Alexandra L.J. Ogilvie Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorNicole A. Kukutsch, Nicole A. Kukutsch Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorSusanne Rößner, Susanne Rößner Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorGerold Schuler, Gerold Schuler Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorJonathan M. Austyn, Jonathan M. Austyn Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, GBSearch for more papers by this author Manfred B. Lutz, Corresponding Author Manfred B. Lutz [email protected] Department of Dermatology, University of Erlangen, Erlangen, GermanyDepartment of Dermatology, University of Erlangen, Hartmannstr.14, D-91052 Erlangen, Germany Fax: +49–9131–853–6417Search for more papers by this authorRakesh M. Suri, Rakesh M. Suri Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, GBSearch for more papers by this authorMasanori Niimi, Masanori Niimi Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorAlexandra L.J. Ogilvie, Alexandra L.J. Ogilvie Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorNicole A. Kukutsch, Nicole A. Kukutsch Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorSusanne Rößner, Susanne Rößner Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorGerold Schuler, Gerold Schuler Department of Dermatology, University of Erlangen, Erlangen, GermanySearch for more papers by this authorJonathan M. Austyn, Jonathan M. Austyn Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, GBSearch for more papers by this author First published: 25 August 2000 https://doi.org/10.1002/1521-4141(200007)30:7<1813::AID-IMMU1813>3.0.CO;2-8Citations: 377 M.B. Lutz, R.M. Suri, G. Schuler and J.M. Austyn contributed equally to this study. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Dendritic cells (DC) were cultured from mouse bone marrow (BM) progenitors in low concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) (GMlo DC) by two different protocols. The phenotype and functional properties of these GMlo DC were compared to those of standard BM-DC cultures generated in high concentrations of GM-CSF (GMhi DC) or in low GM-CSF plus IL-4 (GMlo/IL-4 DC). An effect of IL-4 on maturation was observed only at low but not high doses of GM-CSF. Compared to mature DC, GMlo DC were phenotypically immature, weak stimulators of allogeneic and peptide-specific T cell responses, but substantially more potent in presentation of native protein. Immature GMlo DC were resistant to maturation by lipopolysaccharide, TNF-α or anti-CD40 monoclonal antibodies, as the expression of co-stimulatory molecules was not increased, and stimulatory activity in oxidative mitogenesis was not enhanced. These maturation-resistant immature GMlo DC induced T cell unresponsiveness in vitro and in vivo. GMlo DC also prolonged haplotype-specific cardiac allograft survival (from 8 days to >100 days median survival time) when they were administered 7 days (but not 3, 14 or 28 days) before transplantation. Our findings may have important implications for future studies in T cell tolerance induction in vivo. Citing Literature Volume30, Issue7July 2000Pages 1813-1822 RelatedInformation