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.
Pittsburgh Transplantation Institute, University of Pittsburgh, Pennsylvania 15213, USA.
C
C
Rastellini
L
L
Lu
C
C
Ricordi
T E
TE
Starzl
A S
AS
Rao
A W
AW
Thomson
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