Dendritic cells are required for effective cross-presentation in the murine liver Journal Article
| Authors: | Plitas, G.; Burt, B. M.; Stableford, J. A.; Nguyen, H. M.; Welles, A. P.; DeMatteo, R. P. |
| Article Title: | 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. |
| Keywords: | controlled study; protein expression; promoter region; nonhuman; cd8+ t lymphocyte; cell proliferation; t-lymphocytes; animal cell; mouse; phenotype; animals; mice; mice, knockout; animal tissue; dendritic cell; protein; mice, inbred c57bl; transgenic mouse; liver; dendritic cells; antigen; adoptive transfer; liver cell; antigen presenting cell; t lymphocyte activation; diphtheria toxin; cross presentation; cross-priming; cd40 antigen; glycoprotein p 15095; liver antigen; ovalbumin |
| Journal Title: | Hepatology |
| Volume: | 47 |
| Issue: | 4 |
| ISSN: | 0270-9139 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2008-04-01 |
| Start Page: | 1343 |
| End Page: | 1351 |
| Language: | English |
| DOI: | 10.1002/hep.22167 |
| PUBMED: | 18213574 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: HPTLD" - "Source: Scopus" |
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