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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 + CD3 int natural killer T cells. The expression of ICOS was up-regulated on CD4 + CD3 bright 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.

Original languageEnglish
Pages (from-to)1115-1118
Number of pages4
JournalTransplantation
Volume75
Issue number8
DOIs
Publication statusPublished - Apr 27 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Transplantation

Fingerprint Dive into the research topics of 'Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator'. Together they form a unique fingerprint.

Cite this