Impaired recall of CD8 memory T cells in immunologically privileged tissue
Impaired recall of CD8 memory T cells in immunologically privileged tissue
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DOI：
10.4049/jimmunol.174.3.1165
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发表时间：
2005-02-01
影响因子：
4.4
通讯作者：
Lakkis, FG
中科院分区：
文献类型：
--
作者：
Dai, ZH;Nasr, IW;Lakkis, FG
外来Ags进入免疫特权部位，如眼睛、大脑和睾丸，会持续很长一段时间。而相同的Ags在常规位点会迅速消除。因此，免疫特权为病原体和肿瘤细胞提供了不必要的避难所，但对同种异体移植物的存活是有益的。在这项研究中，我们通过研究CD8记忆T细胞介导的胰岛异体移植在糖尿病小鼠睾丸（特权器官）或肾包膜（非特权部位）下的排斥反应，询问记忆T细胞是否可以消除沉积在免疫特权部位的外来Ags。我们发现CD8记忆T细胞对睾丸内移植的排斥率明显低于对肾内移植的排斥率。睾丸中延迟的移植排斥反应不是由于记忆T细胞归巢或增殖减少，而是由于它们在该部位的凋亡增加。细胞凋亡是由两个TNFR家族成员共同作用介导的。激活记忆T细胞，Fas和CD30的上调。因此，记忆T细胞调查免疫特权组织，但受制于这些部位存在的免疫抑制机制。
Foreign Ags that enter immunologically privileged sites such as the eye, brain, and testis persist for an extended period of time. whereas the same Ags are rapidly eliminated at conventional sites. Immune privilege, therefore, pro-tides unwanted refuge for pathogens and tumor cells but is beneficial for the survival of allogeneic grafts. In this study, we asked whether memory, T cells can eliminate foreign Ags deposited at an immunologically privileged site by studying CD8 memory T cell-mediated rejection of pancreatic islet allografts placed either in the testis (a privileged organ) or under the kidney capsule (a nonprivileged site) of diabetic mice. We found that CD8 memory T cells reject intratesticular grafts at a significantly slower rate than the rejection of intrarenal grafts. Delayed graft rejection in the testis was not due to reduced homing or proliferation of memory T cells but due to their increased apoptosis at that site. Apoptosis was mediated by the combined actions of two TNFR family members that are. up-regulated on activated memory T cells, Fas, and CD30. Therefore, memory T cells survey immunologically privileged tissues but are subject to the immunosuppressive mechanisms present at these sites.