Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo
Combined TLR/CD40 stimulation mediates potent cellular immunity by regulating dendritic cell expression of CD70 in vivo
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DOI：
10.4049/jimmunol.178.3.1564
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Kedl, Ross M.
中科院分区：
文献类型：
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作者：
Sanchez, Phillip J.;McWilliams, Jennifer A.;Kedl, Ross M.
我们之前的研究表明，TLR和CD40激动剂的联合免疫(TLR/CD40激动剂联合免疫)导致抗原特异性CD8 T细胞的扩增比单独使用其中一个激动剂所观察到的扩增指数更大。我们现在表明，T细胞这种扩张背后的机制是树突状细胞上CD70的调节表达。与之前的体外实验结果不同，体内树突状细胞上CD70的表达需要TLR/CD40的联合刺激，而单独刺激其中一条途径并不能显著诱导CD70的表达。此外，TLR/CD40激动剂联合免疫后CD8(+)T细胞的指数扩增依赖于CD70。因此，从先天刺激(TLR)到获得性免疫的转变受CD70表达的调控。
We previously showed that immunization with a combination of TLR and CD40 agonists (combined TLR/CD40 agonist immunization) resulted in an expansion of Ag-specific CD8 T cells exponentially greater than the expansion observed to immunization with either agonist alone. We now show that the mechanism behind this expansion of T cells is the regulated expression of CD70 on dendritic cells. In contrast to previous results in vitro, the expression of CD70 on dendritic cells in vivo requires combined TLR/CD40 stimulation and is not significantly induced by stimulation of either pathway alone. Moreover, the exponential expansion of CD8(+) T cells following combined TLR/CD40 agonist immunization is CD70 dependent. Thus, the transition from innate stimuli (TLRs) to adaptive immunity is controlled by the regulated expression of CD70.