A ROLE FOR CD95 LIGAND IN PREVENTING GRAFT-REJECTION
A ROLE FOR CD95 LIGAND IN PREVENTING GRAFT-REJECTION
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DOI：
10.1038/377630a0
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发表时间：
1995-10-19
期刊：
影响因子：
64.8
通讯作者：
DUKE, RC
中科院分区：
文献类型：
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作者：
BELLGRAU, D;GOLD, D;DUKE, RC
睾丸是一个显著的免疫豁免部位，长期以来因其能够支持同种异体和异种组织移植而闻名（1 - 4）。在此我们研究了睾丸免疫豁免的分子基础。来自能够表达功能性CD95（Fas或Ape - 1）配体的小鼠的睾丸移植物（5 - 8）在同种异体动物的肾囊下移植时可无限期存活，然而来自表达无功能配体的gld突变小鼠的睾丸移植物（8，9）则被排斥。对睾丸的进一步分析表明，CD95配体信使RNA由睾丸支持细胞组成性表达，并且来自正常小鼠而非gld小鼠的支持细胞在移植到同种异体受者体内时可被接受。睾丸中CD95配体的表达可能通过诱导表达CD95的、因移植物抗原而活化的受体T细胞凋亡来发挥作用。这些发现表明CD95配体可用于创建适用于多种移植用途的免疫豁免组织。
TESTIS is a remarkable immune-privileged site, long known for its ability to support allogeneic and xenogeneic tissue transplants(1-4). Here we have investigated the molecular basis for testis immune privilege. Testis grafts derived from mice that can express functional CD95 (Fas or Ape-1) ligand(5-8) survived indefinitely when transplanted under the kidney capsule of allogeneic animals, whereas testis grafts derived from mutant gld mice, which express non-functional ligands(8,9), were rejected. Further analysis of testis showed that CD95 ligand messenger RNA is constitutively expressed by testicular Sertoli cells, and that Sertoli cells from normal mice, but not gld mice, were accepted when transplanted into allogeneic recipients. CD95 ligand expression in the testis probably acts by inducing apoptotic cell death of CD95-expressing, recipient T cells activated in response to graft antigens. These findings indicate that CD95 ligand could be used to create immune-privileged tissue for a variety of transplant uses.