Sanchez Phillip J, McWilliams Jennifer A, Haluszczak Catherine, Yagita Hideo, Kedl Ross M
Integrated Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
J Immunol. 2007 Feb 1;178(3):1564-72. doi: 10.4049/jimmunol.178.3.1564.
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.
我们之前的研究表明，用Toll样受体（TLR）和CD40激动剂联合免疫（联合TLR/CD40激动剂免疫）可导致抗原特异性CD8 T细胞的扩增，其扩增程度比单独使用任何一种激动剂免疫所观察到的扩增程度呈指数级增加。我们现在表明，T细胞这种扩增背后的机制是树突状细胞上CD70的调控表达。与之前的体外研究结果相反，体内树突状细胞上CD70的表达需要联合TLR/CD40刺激，单独刺激任何一条途径都不会显著诱导其表达。此外，联合TLR/CD40激动剂免疫后CD8(+) T细胞的指数级扩增是依赖CD70的。因此，从先天刺激（TLRs）到适应性免疫的转变是由CD70的调控表达所控制的。
