Dendritic cells are required for effective cross-presentation in the murine liver

Abstract

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 CD11chigh 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. Conclusion: 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. Copyright © 2008 by the American Association for the Study of Liver Diseases.