| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Hepatopancreatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and
Laboratory of Cellular Immunobiology and Adult Allogeneic Bone Marrow Transplantation Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065
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+ DCs represented the most prevalent liver DC subset, whereas the majority of peripheral blood DCs were CD16+. 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+ 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+CD25+FoxP3+ 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants DK068346 and AI70658, (to R.P.D.), CA083070 (to J.W.Y.), Louis Berkowitz Family Foundation (to R.P.D.), and the New York State Empire Clinical Research Investigator Program (to J.A.S.).
2 Z.M.B. and J.A.S. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center, Box 203, 1275 York Avenue, New York, NY 10065. E-mail address: dematter{at}mskcc.org
4 Abbreviations used in this paper: NPC, nonparenchymal cell; DC, dendritic cell; lin, lineage; MoDC, monocyte-derived DC; Treg, T regulatory cell.
This article has been cited by other articles:
|
|
 |
|
  A. Castellaneta, T. L. Sumpter, L. Chen, D. Tokita, and A. W. Thomson NOD2 Ligation Subverts IFN-{alpha} Production by Liver Plasmacytoid Dendritic Cells and Inhibits Their T Cell Allostimulatory Activity via B7-H1 Up-Regulation J. Immunol., December 1, 2009; 183(11): 6922 - 6932. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Burt, G. Plitas, Z. Zhao, Z. M. Bamboat, H. M. Nguyen, B. Dupont, and R. P. DeMatteo The Lytic Potential of Human Liver NK Cells Is Restricted by Their Limited Expression of Inhibitory Killer Ig-Like Receptors J. Immunol., August 1, 2009; 183(3): 1789 - 1796. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
