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


CONCLUSIONS
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.
Nakamura
Yoshiichiroh
Y
Department of Surgery I, Fukuoka University School of Medicine, Fukuoka, Japan.
Yasunami
Yohichi
Y
Satoh
Masayuki
M
Hirakawa
Eiji
E
Katsuta
Hitoshi
H
Ono
Junko
J
Kamada
Masafumi
M
Todo
Satoru
S
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Ikeda
Seiyo
S
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004357:Drug Synergism; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects*; D060889:Inducible T-Cell Co-Stimulator Protein; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000293:injuries; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016559:Tacrolimus / Q000494:pharmacology; D015854:Up-Regulation
D000906:Antibodies; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D016559:Tacrolimus