Dendritic cells are required for effective cross-presentation in the murine liver.
The liver harbors a diversity of cell types that have been reported to stimulate T cells. Although most hepatic dendritic cells are immature, a small population of CD11c(high) conventional dendritic cells (cDCs) exists that expresses high levels of costimulatory molecules. We sought to determine the relative contribution of cDCs to cross-presentation by the liver. In vitro, liver nonparenchymal cells (NPCs) depleted of cDCs induced only minimal proliferation and activation of antigen-specific CD8(+) T cells when loaded with soluble protein antigen. Using a transgenic mouse with the CD11c promoter driving expression of the human diphtheria toxin receptor, we found that selective depletion of cDCs in vivo reduced the number and activation of antigen-specific CD8(+) T cells in the liver after intravenous administration of soluble protein antigen. Adoptive transfer of DCs, but not CD40 stimulation, restored the hepatic T-cell response.


CONCLUSIONS
Our findings indicate that the ability of the liver to effectively cross-present soluble protein to antigen-specific CD8(+) T cells depends primarily on cDCs. Despite costimulation, other resident liver antigen-presenting cells cannot compensate for the absence of cDCs.
Plitas
George
G
Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Burt
Bryan M
BM
Stableford
Jennifer A
JA
Nguyen
Hoang M
HM
Welles
Alexander P
AP
DeMatteo
Ronald P
RP
D000818:Animals; D045142:Cross-Priming / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D008099:Liver / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin; D010641:Phenotype; D013601:T-Lymphocytes / Q000502:physiology*
D010047:Ovalbumin