Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, USA.
Cell Immunol. 2010;264(2):119-26. doi: 10.1016/j.cellimm.2010.05.008. Epub 2010 Jun 14.
To better understand the relative efficiencies of using different TLR ligand-activated DCs to induce human CD4(+) T lymphocyte responses, human DCs were activated with two viral and two bacterial TLR ligands, and their production of IL12, TNFalpha, and IL10 was examined. While the two viral TLR ligands (ssRNA and dsRNA) induced DC production of detectable levels of IL12p70, DCs activated by the two bacterial TLR ligands (LPS and flagellin) induced increased proliferation of human allogeneic naïve CD4(+) T cells. dsRNA-activated DCs induced increased Th1 and decreased Th2 differentiation, resulting in extremely polarized responses relative to those induced by unstimulated and other TLR ligand-activated DCs. Neutralization of IL12p70 abrogated most of the Th1 skewing induced by all TLR ligand-activated moDCs. Collectively, these results demonstrate that dsRNA-activated DCs induce more highly polarized human Th1 responses than the other TLR ligand-activated DCs tested here. These results have implications for TLR ligands in immunotherapy.
为了更好地理解使用不同 TLR 配体激活的 DC 诱导人 CD4(+)T 淋巴细胞反应的相对效率，用两种病毒和两种细菌 TLR 配体激活人 DC，并检测其产生的 IL12、TNFalpha 和 IL10。两种病毒 TLR 配体（ssRNA 和 dsRNA）诱导 DC 产生可检测水平的 IL12p70，而两种细菌 TLR 配体（LPS 和鞭毛蛋白）激活的 DC 诱导人同种异体幼稚 CD4(+)T 细胞的增殖增加。dsRNA 激活的 DC 诱导 Th1 分化增加和 Th2 分化减少，导致与未刺激和其他 TLR 配体激活的 DC 诱导的反应相比，具有极度极化的反应。IL12p70 的中和消除了所有 TLR 配体激活的 moDC 诱导的大部分 Th1 偏斜。总之，这些结果表明 dsRNA 激活的 DC 诱导比这里测试的其他 TLR 配体激活的 DC 更高度极化的人 Th1 反应。这些结果对 TLR 配体在免疫治疗中的应用具有重要意义。
