Doxsee Christie L, Riter Tony R, Reiter Michael J, Gibson Shelia J, Vasilakos John P, Kedl Ross M
Department of Pharmacology, 3 M Pharmaceuticals, St Paul, MN 55144, USA.
J Immunol. 2003 Aug 1;171(3):1156-63. doi: 10.4049/jimmunol.171.3.1156.
IL-12 and TNF-alpha production by dendritic cells (DCs) is a critical step in the initiation of local inflammation and adaptive immune responses. We show in this study that a small molecule immune response modifier that is a Toll-like receptor 7 (TLR7) agonist induces IL-12 and TNF-alpha production from murine CD11c(+)CD11b(+)CD8(-) DCs, a subset not previously known for this activity. Stimulation of these DCs through TLR7 in vivo induces significant cytokine production even 12 h after initial stimulation, as well as migration of the DC into T cell zones of the lymphoid tissue. In contrast, stimulation through TLR4 and TLR9 induced IL-12 production predominantly from CD8(+) DCs, consistent with previously published data. All TLR stimuli induced the increase in surface expression of the activation markers B7-1, B7-2, and class II in both CD8(+) and CD8(-) DCs, demonstrating that CD8(+) DCs do respond to TLR7-mediated stimuli. To date this is the only known stimuli to induce preferential cytokine production from CD8(-) DCs. Given the efficacy of TLR7 agonists as antiviral agents, the data collectively indicate that stimulation of CD8(-) DCs through TLR7 most likely plays a role in the generation of antiviral immune responses.
树突状细胞（DCs）产生白细胞介素-12（IL-12）和肿瘤坏死因子-α（TNF-α）是局部炎症启动和适应性免疫反应中的关键步骤。我们在本研究中表明，一种作为Toll样受体7（TLR7）激动剂的小分子免疫反应调节剂可诱导小鼠CD11c(+)CD11b(+)CD8(-) DCs产生IL-12和TNF-α，该亚群此前未知具有此活性。在体内通过TLR7刺激这些DCs，即使在初次刺激后12小时仍能诱导显著的细胞因子产生，以及DCs迁移至淋巴组织的T细胞区。相比之下，通过TLR4和TLR9刺激主要诱导CD8(+) DCs产生IL-12，这与先前发表的数据一致。所有TLR刺激均诱导CD8(+)和CD8(-) DCs表面激活标志物B7-1、B7-2和II类分子的表达增加，表明CD8(+) DCs确实对TLR7介导的刺激有反应。迄今为止，这是唯一已知能诱导CD8(-) DCs优先产生细胞因子的刺激物。鉴于TLR7激动剂作为抗病毒药物的有效性，这些数据共同表明通过TLR7刺激CD8(-) DCs很可能在抗病毒免疫反应的产生中发挥作用。
