Development of the new immunological tolerance induction which uses Notch ligands in islet transplantation

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It has been shown that the Delta family, which is one of Notch ligand family, control the immune response in positive direction. But, as for the function in immune response of the Jagged family, which is another Notch ligand family, the part which still does not become clear is a lot. This time we have focused on the function and the especially immune response control action in the immune response of Jagged 1. With the result of in vitro; in the Delta1 revelation dendritic cell, it could recognize the reinforcement of cell proliferation, but it had decreased by comparison with the contrast group in the Jagged I revelation dendritic cell proliferation (reported in the 106th annual congress of Japan Surgical Society). From this research, the possibility was shown that Jagged 1 has controlled immune response in negative direction, and through the T lymphocyte the donor unique low reactivity can be introduced in transplantation immunity.With the result of in vivo, in the A20 cell which introduces Jagged2, the tumor area reduced by comparison with control. In addition, the secretion of IFN- and Granzyme B increased by introducing the Jagged2 gene, could recognize the activation of NK cell. (Proc Natl Acad Sci USA (2008) in press)From these results, it was recognized that Notch ligands could participate not only transplantation immunity but also tumor immunity, and was suggested the possibility of the controlling the rejection in transplantation by Notch ligands and the development of the new remedy for the tumor.