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

Fingerprint

Inducible T-Cell Co-Stimulator Protein
Allografts
Liver
T-Lymphocytes
Antibodies
Natural Killer T-Cells
Tacrolimus
Streptozocin
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator. / Nakamura, Yoshiichiroh; Yasunami, Yohichi; Satoh, Masayuki; Hirakawa, Eiji; Katsuta, Hitoshi; Ono, Junko; Kamada, Masafumi; Todo, Satoru; Nakayama, Toshinuri; Taniguchi, Masaru; Ikeda, Seryo.

In: Transplantation, Vol. 75, No. 8, 27.04.2003, p. 1115-1118.

Research output: Contribution to journalArticle

Nakamura, Y, Yasunami, Y, Satoh, M, Hirakawa, E, Katsuta, H, Ono, J, Kamada, M, Todo, S, Nakayama, T, Taniguchi, M & Ikeda, S 2003, 'Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator', Transplantation, vol. 75, no. 8, pp. 1115-1118. https://doi.org/10.1097/01.TP.0000063705.80764.0F
Nakamura, Yoshiichiroh ; Yasunami, Yohichi ; Satoh, Masayuki ; Hirakawa, Eiji ; Katsuta, Hitoshi ; Ono, Junko ; Kamada, Masafumi ; Todo, Satoru ; Nakayama, Toshinuri ; Taniguchi, Masaru ; Ikeda, Seryo. / Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator. In: Transplantation. 2003 ; Vol. 75, No. 8. pp. 1115-1118.
@article{b48435f8aec54e078822f2c9859ce854,
title = "Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator",
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.",
author = "Yoshiichiroh Nakamura and Yohichi Yasunami and Masayuki Satoh and Eiji Hirakawa and Hitoshi Katsuta and Junko Ono and Masafumi Kamada and Satoru Todo and Toshinuri Nakayama and Masaru Taniguchi and Seryo Ikeda",
year = "2003",
month = "4",
day = "27",
doi = "10.1097/01.TP.0000063705.80764.0F",
language = "English",
volume = "75",
pages = "1115--1118",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Acceptance of islet allografts in the liver of mice by blockade of an inducible costimulator

AU - Nakamura, Yoshiichiroh

AU - Yasunami, Yohichi

AU - Satoh, Masayuki

AU - Hirakawa, Eiji

AU - Katsuta, Hitoshi

AU - Ono, Junko

AU - Kamada, Masafumi

AU - Todo, Satoru

AU - Nakayama, Toshinuri

AU - Taniguchi, Masaru

AU - Ikeda, Seryo

PY - 2003/4/27

Y1 - 2003/4/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0037469064&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037469064&partnerID=8YFLogxK

U2 - 10.1097/01.TP.0000063705.80764.0F

DO - 10.1097/01.TP.0000063705.80764.0F

M3 - Article

C2 - 12717187

AN - SCOPUS:0037469064

VL - 75

SP - 1115

EP - 1118

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 8

ER -