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CD95 (FAS) LIGAND AND IMMUNE PRIVILEGED TISSUE

CD95 (FAS) 配体和免疫特权组织

基本信息

批准号：
6124391
负责人：
RICHARD C DUKE
金额：
$ 20.96万
依托单位：
ELEANOR ROOSEVELT INST FOR CANCER RES
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-12-01 至 2001-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6124391
关键词：
CD95 molecule gene expression immune tolerance /unresponsiveness immunomodulators laboratory mouse laboratory rat ligands pancreatic islets polymerase chain reaction spleen testis tissue /cell culture transfection transplantation immunology

项目摘要

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?

虽然等待人体组织（同种异体移植）的患者人数由于缺乏合适的捐赠者，可以进行的移植。非人组织（异种）来源不能被使用，因为它被暴力拒绝。接受者也不是同种异体移植物都能完全恢复正常生活终身需要免疫抑制来防止移植物排斥，易受感染和癌症。因此，非常需要新的预防同种异体移植物和异种移植物排斥免疫抑制剂没有明显的副作用。睾丸长期以来一直被称为“免疫特权”网站，同种异体移植物和异种移植物可以被成功地移植。我们有发现免疫赦免是由免疫调节因子介导的，一种叫做CD95配体的蛋白质，由睾丸支持细胞产生。下面描述的实验将进一步表征 CD95配体在移植环境中免疫抑制特性小鼠此外，这些研究也将开始解决我们的长期目标是创造通用的“CD95配体保护”供体组织，缓解目前人体组织短缺的问题。具体来说，我们将问： L. CD95配体能保护组织免受预先存在的抗移植免疫吗回应？ 2.表达CD95配体的组织能保护不表达CD95L的组织吗移植在同一个部位引起的排斥反应吗 3.表达CD95配体的组织能否诱导对移植物抗原的耐受使得随后的不表达CD95L的组织移植物防止移植排斥反应吗 4.编码CD 95配体的基因能否用于创造免疫特权适合移植的组织