Immune regulatory activity of liver-derived dendritic cells generated in vivo.
Hepatic tolerance is demonstrated by spontaneous acceptance of liver allografts in mice. Hepatic dendritic cells (DC) play a crucial role in determining immunity or tolerance. In this study, we adopted an approach to transfect gene(s) into the mouse liver by tail-vein injection of plasmid-carrying genes. Transfection with GM-CSF expanded liver CD11c+ myeloid DC (LMDC), while liver B220+CD11c- lymphoid DC (LLDC) were expanded after transfection of IL-3 and CD40L. Flow analysis revealed that these liver DC subsets were phenotypically mature following overnight culture. However, in contrast to LMDC, LLDC induced hyporesponsiveness in allogeneic T-cells, with suppressed secretion of both IL-2 and IFN-gamma, and prolonged cardiac allograft survival. This immune regulatory DC population in the liver may play a role in modulating T-cell immunity in the liver.
Wu
Wenhan
W
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
Zheng
Ning
N
Wang
Yalan
Y
Fung
John J
JJ
Lu
Lina
L
Qian
Shiguang
S
D000818:Animals; D023201:CD40 Ligand / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D016027:Heart Transplantation / Q000276:immunology*; D007377:Interleukin-3 / Q000502:physiology*; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014162:Transfection; D023001:Transplantation Tolerance / Q000276:immunology
D007377:Interleukin-3; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor