CD95 (FAS) LIGAND AND IMMUNE PRIVILEGED TISSUE

CD95 (FAS) 配体和免疫特权组织

• 批准号: 2837474
• 负责人: RICHARD C DUKE
• 金额: $ 7.3万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2837474
• 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

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?

而等待人体组织（同种异体移植物）的患者数量 持续增加，缺乏合适的捐助者限制了 可以进行的移植手术。来自非人类（异种）的组织 来源不能使用，因为它被强烈拒绝。收件人也不是 的同种异体移植物恢复了完全正常的生活。终身 需要免疫抑制来防止移植排斥离开患者 容易受到感染和癌症。因此非常需要新的 预防同种异体移植和异种移植排斥的免疫抑制剂 无明显副作用。 睾丸长期以来被认为是一个“免疫特权”场所， 同种异体移植物和异种移植物都可以成功移植。我们有 发现免疫特权是由免疫调节介导的 称为 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 配体在移植环境中的免疫抑制特性 老鼠。此外，这些研究也将开始解决我们的长期问题 创建通用的“CD95配体保护”供体组织的目标 缓解目前人体组织短缺的问题。具体来说，我们将 问： 湖CD95 配体能否保护组织免受先前存在的抗移植免疫的影响 回复？ 2. CD95配体表达组织可以保护非CD95L表达组织吗 因移植排斥而移植到同一部位？ 3. CD95配体表达组织能否诱导对移植物抗原的耐受 以便随后的非 CD95L 表达组织移植 免受移植排斥？ 4. 编码CD95配体的基因能否用于创建免疫特权 适合移植的组织？