Requirement for natural killer T (NKT) cells in the induction of allograft tolerance.
In this study, we investigated the role of Valpha14 natural killer T (NKT) cells in transplant immunity. The ability to reject allografts was not significantly different between wild-type (WT) and Valpha14 NKT cell-deficient mice. However, in models in which tolerance was induced against cardiac allografts by blockade of lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions, long-term acceptance of the grafts was observed only in WT but not Valpha14 NKT cell-deficient mice. Adoptive transfer with Valpha14 NKT cells restored long-term acceptance of allografts in Valpha14 NKT cell-deficient mice. The critical role of Valpha14 NKT cells to mediate immunosuppression was also observed in vitro in mixed lymphocyte cultures in which lymphocyte function-associated antigen-1/intercellular adhesion molecule-1 or CD28/B7 interactions were blocked. Experiments using IL-4- or IFN-gamma-deficient mice suggested a critical contribution of IFN-gamma to the Valpha14 NKT cell-mediated allograft acceptance in vivo. These results indicate a critical contribution of Valpha14 NKT cells to the induction of allograft tolerance and provide a useful model to investigate the regulatory role of Valpha14 NKT cells in various immune responses.
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Science City, Ibaraki 305-8575, Japan. seinok@md.tsukuba.ac.jp
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Seino
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Fukao
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Muramoto
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Yanagisawa
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Takada
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Kakuta
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Iwakura
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Van Kaer
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Takeda
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Nakayama
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Taniguchi
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Bashuda
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Yagita
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Okumura
D000222:Adaptation, Physiological / Q000276:immunology*; D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014184:Transplantation, Homologous
D018106:CD28 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1