TOKITA Daisuke    Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice.
Journal	Formal name：Journal of immunology (Baltimore, Md. : 1950) Abbreviation：J Immunol ISSN code：00221767/00221767
Domestic / Foregin	Foregin
Volume, Issue, Page	175(1),pp.139-46
Author and coauthor	Onoe Takashi, Ohdan Hideki, Tokita Daisuke, Shishida Masayuki, Tanaka Yuka, Hara Hidetaka, Zhou Wendy, Ishiyama Kohei, Mitsuta Hiroshi, Ide Kentaro, Asahara Toshimasa
Publication date	2005/07
Summary	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.
DOI	10.4049/jimmunol.175.1.139
PMID	15972640