Human liver dendritic cells promote T cell hyporesponsiveness Journal Article
| Authors: | Bamboat, Z. M.; Stableford, J. A.; Plitas, G.; Burt, B. M.; Nguyen, H. M.; Welles, A. P.; Gonen, M.; Young, J. W.; DeMatteo, R. P. |
| Article Title: | Human liver dendritic cells promote T cell hyporesponsiveness |
| Abstract: | The liver is believed to promote tolerance, which may be beneficial due to its constant exposure to foreign Ags from the portal circulation. Although dendritic cells (DCs) are critical mediators of immune responses, little is known about human liver DCs. We compared freshly purified liver DCs from surgical specimens with autologous blood DCs. Liver and blood DCs were equally immature, but had distinct subset compositions. BDCA-1<sup>+</sup> DCs represented the most prevalent liver DC subset, whereas the majority of peripheral blood DCs were CD16<sup>+</sup>. Upon TLR4 ligation, blood DCs secreted multiple proinflammatory cytokines, whereas liver DCs produced substantial amounts of IL-10. Liver DCs induced less proliferation of allogeneic T cells both in a primary MLR and after restimulation. Similarly, Ag-specific CD4<sup>+</sup> T cells were less responsive to restimulation when initially stimulated by autologous liver DCs rather than blood DCs. In addition, liver DCs generated more suppressive CD4<sup>+</sup> CD25<sup>+</sup>FoxP3<sup>+</sup> T regulatory cells and IL-4-producing Th2 cells via an IL-10-dependent mechanism. Our findings are critical to understanding hepatic immunity and demonstrate that human liver DCs promote immunologic hyporesponsiveness that may contribute to hepatic tolerance. Copyright © 2009 by The American Association of Immunologists, Inc. |
| Keywords: | controlled study; unclassified drug; human cell; flow cytometry; transcription factor foxp3; lymphocyte proliferation; t lymphocyte; t-lymphocytes; cytology; dendritic cell; interleukin 10; interleukin 4; bdca4 antigen; cd16 antigen; membrane antigen; toll like receptor 4; cytokine; blood; cd4+ cd25+ t lymphocyte; immunological tolerance; liver; regulatory t lymphocyte; th2 cell; antigen presentation; biosynthesis; immunology; lymphocyte activation; mixed lymphocyte culture; cytokines; dendritic cells; immune tolerance; lymphocyte culture test, mixed |
| Journal Title: | Journal of Immunology |
| Volume: | 182 |
| Issue: | 4 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2009-02-15 |
| Start Page: | 1901 |
| End Page: | 1911 |
| Language: | English |
| DOI: | 10.4049/jimmunol.0803404 |
| PUBMED: | 19201843 |
| PROVIDER: | scopus |
| PMCID: | PMC3254024 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 17" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus" |
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