The CD8alpha(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens.
The CD8alpha(+) dendritic cell is responsible for inducing peripheral self-tolerance to tissue-associated antigens.
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CD8α(+)树突状细胞负责诱导外周组织相关抗原的自身耐受。
DOI：
10.1084/jem.20020861
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发表时间：
2002-10-21
影响因子：
15.3
通讯作者：
Heath, William R
中科院分区：
文献类型：
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作者：
Belz, Gabrielle T;Behrens, Georg M N;Smith, Chris M;Miller, Jacques F A P;Jones, Claerwen;Lejon, Kristina;Fathman, C Garrison;Mueller, Scott N;Shortman, Ken;Carbone, Francis R;Heath, William R
我们之前描述了维持外周自我耐受性的机制。这涉及骨髓来源的细胞类型交叉呈递组织相关抗原，刺激自身反应性CD8 T细胞的增殖和最终缺失。这个过程被称为交叉耐受。在此，我们将负责诱导交叉耐受的难以捉摸的细胞类型描述为CD8 α +树突状细胞（DC）。为了实现这一目标，产生了在大鼠胰岛素启动子（RIP）下表达与单纯疱疹病毒的卵清蛋白和糖蛋白B（g B）的CTL表位连接的黄色荧光蛋白（YFP）的转基因小鼠。尽管YFP的追踪不确定，但使用在遇到抗原时产生β-半乳糖苷酶的高度敏感的gB特异性杂交瘤，能够检测从胰腺淋巴结分离的细胞的抗原呈递。这表明，CD11c + CD8 α +细胞负责交叉耐受，与先前交叉致敏中涉及的DC亚群相同。这些数据表明，CD8 α + DC在对细胞相关抗原的耐受和免疫中起关键作用，提供了一种潜在的机制，通过该机制，细胞毒性T淋巴细胞可以免疫病毒抗原，同时保持对自身的耐受。
We previously described a mechanism for the maintenance of peripheral self-tolerance. This involves the cross-presentation of tissue-associated antigens by a bone marrow–derived cell type that stimulates the proliferation and ultimate deletion of self-reactive CD8 T cells. This process has been referred to as cross-tolerance. Here, we characterize the elusive cell type responsible for inducing cross-tolerance as a CD8α+ dendritic cell (DC). To achieve this aim, transgenic mice were generated expressing yellow fluorescent protein (YFP) linked to CTL epitopes for ovalbumin and glycoprotein B (gB) of herpes simplex virus under the rat insulin promoter (RIP). Although tracking of YFP was inconclusive, the use of a highly sensitive gB-specific hybridoma that produced β-galactosidase on encounter with antigen, enabled detection of antigen presentation by cells isolated from the pancreatic lymph node. This showed that a CD11c+CD8α+ cell was responsible for cross-tolerance, the same DC subset as previously implicated in cross-priming. These data indicate that CD8α+ DCs play a critical role in both tolerance and immunity to cell-associated antigens, providing a potential mechanism by which cytotoxic T lymphocyte can be immunized to viral antigens while maintaining tolerance to self.