CD95 (FAS) LIGAND AND IMMUNE PRIVILEGED TISSUE

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While the number of patients awaiting human tissues (allografts) continues to mount, the paucity of suitable donors limits the number of transplants that can be performed. Tissue from non human (xenogeneic) sources cannot be used since it is violently rejected. Nor are recipients of allografts returned to a completely normal life. Lifelong immunosuppression is required to prevent graft rejection leaving patients susceptible to infections and cancer. Thus there is a great need for new immunosuppressive agents which prevent allograft and xenograft rejection without significant side-effects. Testis has long been known as an "immune privileged" site into which allografts and xenografts can be successfully transplanted. We have discovered that immune privilege is mediated by an immunoregulatory protein called CD95 ligand which is produced by testicular Sertoli cells. The experiments described below will further characterize the immunosuppressive attributes of CD95 ligand in transplant settings in mice. In addition, these studies will also begin to address our long term goal of creating universal "CD95 ligand-protected" donor tissues to alleviate the current shortage of human tissues. Specifically, we will ask: l. Can CD95 ligand protect a tissue from a preexisting anti-graft immune response? 2. Can CD95 ligand-expressing tissue protect non-CD95L-expressing tissue transplanted in the same site from graft rejection? 3. Can CD95 ligand-expressing tissue induce tolerance to graft antigens such that subsequent non-CD95L-expressing tissue transplants are protected from graft rejection? 4. Can the gene encoding CD95 ligand be used to create immune privileged tissue suitable for transplant?