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.

Journal article

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.

Authors: Lutz, M; Suri, R; Niimi, M; Ogilvie, A; Kukutsch, N

• Publication status: Published
• Journal: European journal of immunology
• Volume: 30
• Issue: 7
• Pages: 1813-1822
• Publication date: 2000-07-01
• DOI: 10.1002/1521-4141(200007)30:7<1813::aid-immu1813>3.0.co;2-8
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Dose-Response Relationship, Drug; Heart Transplantation; Cell Differentiation; Immunophenotyping; Graft Survival; Isoantigens; Bone Marrow Cells; Mice, Inbred BALB C; Time Factors; Cells, Cultured; Interleukin-4; Mice; T-Lymphocytes; Granulocyte Macrophage Colony-Stimulating Factors, Recombinant; Mice, Inbred CBA; Adoptive Transfer; Animals; Dendritic Cells