Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator

Yoshiichiroh Nakamura, Yohichi Yasunami, Masayuki Satoh, Eiji Hirakawa, Hitoshi Katsuta, Junko Ono, Masafumi Kamada, Satoru Todo, Toshinuri Nakayama, Masaru Taniguchi, Seryo Ikeda

研究成果: Contribution to journalArticle査読

19 被引用数 (Scopus)

抄録

Background. An inducible costimulator (ICOS) has been found to be a novel costimulator for T-cell activation, although its precise role in transplant immunobiology remains unclear. This study determined whether ICOS plays an essential role in rejection of intrahepatic islet allografts in streptozotocin-induced diabetic mice. Methods. Mononuclear cells in the liver of mice were isolated and examined by flow cytometry with respect to expression of ICOS in association with rejection, and the effects of in vivo treatment with an anti-ICOS antibody on survival of intrahepatic islet allografts were determined. Results. Flow cytometric analysis of mononuclear cells in the liver of normal untreated mice revealed that ICOS is expressed on CD4+CD3int natural killer T cells. The expression of ICOS was up-regulated on CD4+CD3bright T cells and expanded CD8 T cells in the liver in association with rejection. Posttransplant short-term administration of anti-ICOS antibody alone produced a significant prolongation of islet allograft survival. Administration of the antibody in conjunction with a subtherapeutic regimen of FK506 prevented rejection, leading to the acceptance of islet allografts. Conclusion. ICOS has an essential role in rejection of intrahepatic islet allografts and the blockade of ICOS interaction might be a novel approach for preventing islet allograft rejection.

本文言語英語
ページ(範囲)1115-1118
ページ数4
ジャーナルTransplantation
75
8
DOI
出版ステータス出版済み - 4 27 2003
外部発表はい

All Science Journal Classification (ASJC) codes

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