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Natural Killer T-Cells Participate in Rejection of Islet Allografts in the Liver of Mice

¹ Department of Surgery I, Fukuoka University, Fukuoka, Japan
² Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
³ Department of Laboratory Medicine, Fukuoka University, Fukuoka, Japan
⁴ Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan
⁵ Laboratory for Immune Regulation, Riken Research Center for Allergy and Immunology, Yokohama, Japan

Address correspondence and reprint requests to Yohichi Yasunami, MD, Associate Professor, Department of Surgery I, Fukuoka University School of Medicine, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. E-mail: yasunami{at}fukuoka-u.ac.jp

Abbreviations: -GalCer, -galactosylceramide; IFN-, -interferon; IL, interleukin; mAb, monoclonal antibody; NKT, natural killer T; STZ, streptozotocin

A role of natural killer T (NKT) cells in transplant rejection remains unknown. Here, we determined whether NKT cells participate in rejection of islet allografts, using NKT cell–deficient mice. Survival of islet allografts in streptozotocin-induced diabetic CD1d^–/– mice or V14 NKT cell^–/– mice was significantly prolonged without immunosuppression when grafted into the liver, but not beneath the kidney capsule, compared with wild-type mice. Acceptance of intrahepatic islet allografts was achieved in CD1d^–/– mice by a subtherapeutic dose of rapamycin, which was abrogated in conjunction with the transfer of hepatic mononuclear cells from wild-type, but not from CD1d^–/–, mice at islet transplantation. The second islet grafts from a donor-specific, but not from a third-party, strain in CD1d^–/– mice bearing functional islet allografts were accepted without immunosuppression at 120 days after the initial transplantation. These findings demonstrate that NKT cells play a significant role in rejection of islet allografts in the liver of mice, but that NKT cells are not essential for induction of donor-specific unresponsiveness in this model. The current study indicates that NKT cells might be considered as a target for intervention to prevent islet allograft rejection when the liver is the site of transplantation.

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