HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Onoe, T. Articles by Asahara, T. Search for Related Content PubMed PubMed Citation Articles by Onoe, T. Articles by Asahara, T.

Liver Sinusoidal Endothelial Cells Tolerize T Cells across MHC Barriers in Mice ¹

Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

Although livers transplanted across MHC barriers in mice are normally accepted without recipient immune suppression, the underlying mechanisms remain to be clarified. To identify the cell type that contributes to induction of such a tolerance state, we established a mixed hepatic constituent cell-lymphocyte reaction (MHLR) assay. Irradiated C57BL/6 (B6) or BALB/c mouse hepatic constituent cells (HCs) and CFSE-labeled B6 splenocytes were cocultured. In allogeneic MHLR, whole HCs did not promote T cell proliferation. When liver sinusoidal endothelial cells (LSECs) were depleted from HC stimulators, allogeneic MHLR resulted in marked proliferation of reactive CD4⁺ and CD8⁺ T cells. To test the tolerizing capacity of the LSECs toward alloreactive T cells, B6 splenocytes that had transmigrated through monolayers of B6, BALB/c, or SJL/j LSECs were restimulated with irradiated BALB/c splenocytes. Nonresponsiveness of T cells that had transmigrated through allogeneic BALB/c LSECs and marked proliferation of T cells transmigrated through syngeneic B6 or third-party SJL/j LSECs were observed after the restimulation. Transmigration across the Fas ligand-deficient BALB/c LSECs failed to render CD4⁺ T cells tolerant. Thus, we demonstrate that Fas ligand expressed on naive LSECs can impart tolerogenic potential upon alloantigen recognition via the direct pathway. This presents a novel relevant mechanism of liver allograft tolerance. In conclusion, LSECs are capable of regulating a polyclonal population of T cells with direct allospecificity, and the Fas/Fas ligand pathway is involved in such LSEC-mediated T cell regulation.

This article has been cited by other articles:

				K. Elvevold, B. Smedsrod, and I. Martinez The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G391 - G400. [Abstract] [Full Text] [PDF]

				J. Morimoto, X. Tan, R. M. Teague, C. Ohlen, and P. D. Greenberg Induction of Tolerance in CD8+ T Cells to a Transgenic Autoantigen Expressed in the Liver Does Not Require Cross-Presentation J. Immunol., June 1, 2007; 178(11): 6849 - 6860. [Abstract] [Full Text] [PDF]

				D. Tokita, M. Shishida, H. Ohdan, T. Onoe, H. Hara, Y. Tanaka, K. Ishiyama, H. Mitsuta, K. Ide, K. Arihiro, et al. Liver Sinusoidal Endothelial Cells That Endocytose Allogeneic Cells Suppress T Cells with Indirect Allospecificity J. Immunol., September 15, 2006; 177(6): 3615 - 3624. [Abstract] [Full Text] [PDF]