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Dendritic cells (DC) were cultured from mouse bone marrow (BM) progenitors in low concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) (GM(lo) DC) by two different protocols. The phenotype and functional properties of these GM(lo) DC were compared to those of standard BM-DC cultures generated in high concentrations of GM-CSF (GM(hi) DC) or in low GM-CSF plus IL-4 (GM(lo)/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, GM(lo) DC were phenotypically immature, weak stimulators of allogeneic and peptide-specific T cell responses, but substantially more potent in presentation of native protein. Immature GM(lo) DC were resistant to maturation by lipopolysaccharide, TNF-alpha 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 GM(lo) DC induced T cell unresponsiveness in vitro and in vivo. GM(lo) 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.

Original publication

DOI

10.1002/1521-4141(200007)30:7<1813::AID-IMMU1813>3.0.CO;2-8

Type

Journal article

Journal

Eur J Immunol

Publication Date

07/2000

Volume

30

Pages

1813 - 1822

Keywords

Adoptive Transfer, Animals, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Dendritic Cells, Dose-Response Relationship, Drug, Graft Survival, Granulocyte-Macrophage Colony-Stimulating Factor, Heart Transplantation, Immunophenotyping, Interleukin-4, Isoantigens, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Recombinant Proteins, T-Lymphocytes, Time Factors