Dendritic cells, engineered to secrete a T-cell receptor mimic peptide, induce antigen-specific immunosuppression in vivo
Dendritic cells, engineered to secrete a T-cell receptor mimic peptide, induce antigen-specific immunosuppression in vivo
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DOI：
10.1038/nbt842
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发表时间：
2003-08-01
影响因子：
46.9
通讯作者：
Enk, AH
中科院分区：
文献类型：
--
作者：
Mahnke, K;Qian, YJ;Enk, AH
T细胞受体模拟肽（TCRpep）由8个氨基酸的肽组成，与T细胞受体（TCR）链的跨膜区同源，在全身应用后阻断T细胞活化。当树突状细胞（DC）被转导以分泌TCRpep并注射到小鼠中时，观察到免疫抑制的证据。在CD8驱动的变态反应模型中，注射TCRpep转导的DC显著减少炎症，并且在多发性硬化症（实验性自身免疫性脑炎，EAE）的CD4（+）T细胞依赖性模型中，注射分泌TCRpep的DC消除EAE症状并延长存活。这些效应是抗原特异性的，因为不表达相应抗原的转导的DC在变态反应模型以及EAE模型中不能传递保护。因此，这些数据表明，表达TCRpep的DC能够抑制T细胞活化，并且可能是用于在体内诱导抗原特异性免疫抑制的有用工具。
A T-cell receptor mimic peptide (TCRpep) consisting of an 8-amino-acid peptide, homologous to the transmembrane region of the T-cell receptor (TCR) chain, blocks T-cell activation after systemic application. When dendritic cells (DCs) were transduced to secrete the TCRpep and injected into mice, evidence of immunosuppression was observed. In a CD8-driven allergy model, the injection of DCs transduced with the TCRpep reduced inflammation markedly and in a CD4(+) T cell-dependent model of multiple sclerosis (experimental autoimmune encephalitis, EAE), injection of TCRpep-secreting DCs abrogated EAE symptoms and prolonged survival. These effects were antigen specific, because transduced DCs that did not express the respective antigen failed to convey protection in the allergy model as well as in the EAE model. Thus these data show that DCs expressing the TCRpep are able to suppress T-cell activation and might be a useful tool for inducing antigen-specific immune suppression in vivo.