トキタ ダイスケ   TOKITA Daisuke
  時田 大輔
   所属   医学部 医学科(東京女子医科大学病院)
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice.
掲載誌名 正式名:Journal of immunology (Baltimore, Md. : 1950)
略  称:J Immunol
ISSNコード:00221767/00221767
掲載区分国外
巻・号・頁 175(1),pp.139-46
著者・共著者 Onoe Takashi, Ohdan Hideki, Tokita Daisuke, Shishida Masayuki, Tanaka Yuka, Hara Hidetaka, Zhou Wendy, Ishiyama Kohei, Mitsuta Hiroshi, Ide Kentaro, Asahara Toshimasa
発行年月 2005/07
概要 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