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 Induction of endotoxin tolerance inhibits alloimmune responses.
掲載誌名 正式名:Transplant immunology
略  称:Transpl Immunol
ISSNコード:09663274/09663274
掲載区分国外
巻・号・頁 16(3-4),pp.158-65
著者・共著者 Ishiyama Kohei, Ohdan Hideki, Tokita Daisuke, Shishida Masayuki, Tanaka Yuka, Irei Toshimitsu, Asahara Toshimasa
発行年月 2006/11
概要 It was recently reported that the induction of endotoxin tolerance (ET), which is defined as a reduced response to a lipopolysaccharide (LPS) challenge following the first LPS encounter, inhibits major histocompatibility complex (MHC)-restricted antigen presentation. This raises the question whether alloimmune responses can be inhibited by inducing ET in transplant donors. C57BL/6 mice were treated with a low dose of LPS prior to a challenge with a high dose of LPS to induce ET. Hearts from endotoxin-tolerized C57BL/6 mice were transplanted to BALB/c mice. The survival of the endotoxin-tolerized heart allografts was significantly prolonged. By using irradiated splenocytes from C57BL/6 mice and allogeneic splenocytes from BALB/c mice, a mixed lymphocyte reaction (MLR) assay was performed. The MLR assay used CFSE, and revealed that the splenocytes from the endotoxin-tolerized mice failed to induce the proliferation of allogeneic CD4(+) and CD8(+) T cells. Cytokine analyses of the supernatant of the MLR culture using endotoxin-tolerized stimulators revealed a distinct shift in the Th 1/Th 2 balance toward the Th 2-type response. The induction of ET increased the proportion of myeloid-related dendritic cells (DCs) expressing molecules necessary for antigen presentation, which favor the development of a Th 2 response; however, it reduced the proportion of lymphoid-related DCs expressing those molecules, which favor the development of the Th 1 response. Although the relevance of these findings with regard to the prolonged survival of the endotoxin-tolerized heart allografts remains to be elucidated, this is the first study to demonstrate that the induction of ET in donor animals inhibits alloimmune responses.
DOI 10.1016/j.trim.2006.06.002
PMID 17138048