Granulocyte/macrophage colony-stimulating factor-stimulated hepatic dendritic cell progenitors prolong pancreatic islet allograft survival.
Liver-derived dendritic cell (DC) progenitors propagated in liquid culture in granulocyte/macrophage colony-stimulating factor exhibit low levels both of cell surface MHC class II antigens and of counter-receptors for CTLA-4/CD28. They fail to stimulate allogeneic T cells in mixed leukocyte cultures. To evaluate their in vivo functional significance, we determined their influence on survival of pancreatic islet allografts. Cultured B10.BR (H2k;I-E+) mouse liver-derived DC progenitors were injected (2 x 10(6) i.v.) into streptozotocin-diabetic B10 (H2b; I-E-) recipients 7 days before transplantation of pancreatic islets (700 IEq/mouse) from the same donor strain. No immunosuppressive agents were administered. Mean islet allograft survival time was prolonged from 15.3 days (in animals pretreated with syngeneic cells) to 30.3 days (P < 0.001) in mice pretreated with the donor-derived liver cells. In 20% of these animals, islet allograft survival exceeded 60 days. These data suggest that liver-derived DC progenitors may contribute both to the inherent tolerogenicity of the mouse liver and to its capacity to protect other allografts of the same donor strain from rejection.
Rastellini
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Pittsburgh Transplantation Institute, University of Pittsburgh, Pennsylvania 15213, USA.
Lu
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Ricordi
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Starzl
T E
TE
Rao
A S
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Thomson
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AW
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D006085:Graft Survival; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007108:Immune Tolerance; D016130:Immunophenotyping; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
D016178:Granulocyte-Macrophage Colony-Stimulating Factor