Natural killer T-cells participate in rejection of islet allografts in the liver of mice.
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 Valpha14 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.
Toyofuku
Atsushi
A
Department of Surgery I, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Yasunami
Yohichi
Y
Nabeyama
Kentaroh
K
Nakano
Masahiko
M
Satoh
Masayuki
M
Matsuoka
Nobuhide
N
Ono
Junko
J
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Tanaka
Masao
M
Ikeda
Seiyo
S
D019264:Adoptive Transfer; D000818:Animals; D018949:Antigens, CD1 / Q000235:genetics; D017353:Gene Deletion; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007668:Kidney / Q000166:cytology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D015854:Up-Regulation
D018949:Antigens, CD1; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma; D020123:Sirolimus