The aim of this study is to extend observations on transplantation tolerance induction in mice to primates. Out laboratory has demonstrated that donor specific transfusion and treatment with anti-CD4OL antibody results in permanent islet allograft tolerance and prolonged skin allograft survival in mice. We have also observed that this system can be applied for prolongation of xenografts of rat tissues into mice. It is uncertain, however, whether this transplantation tolerance induction protocol use din mice will be effective in humans. A humanized antibody to the human CD4OL antibody has been synthesized and made available for the proposed studies in monkeys as a preclinical assessment of the feasibility of using it for human transplantation. This antibody reacts with CD4OL on monkey lymphocytes, allowing us to test the combination treatment protocol of donor specific lymphocyte transfusion and anti-CD4OL antibody administration for tolerance induction in primates. Many tolerance protocols that are effective in mice are not translatable to higher vertebrates, including primates. Prior to the clinical application of this transplantation procedure, the feasibility of its effectiveness must be tested in primates. This study is specifically designed to determine whether the combination treatment of anti-CD4OL antibody and donor specific transfusion will induce transplantation tolerance to kidney allografts in primates.
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