The TLR9 ligand CpG ODN 2006 is a poor adjuvant for the induction of de novo CD8+ T-cell responses in vitro
The TLR9 ligand CpG ODN 2006 is a poor adjuvant for the induction of de novo CD8+ T-cell responses in vitro
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DOI：
10.1038/s41598-020-67704-0
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发表时间：
2020-07-15
影响因子：
4.6
通讯作者：
Nicoli, Francesco
中科院分区：
文献类型：
--
作者：
Papagno, Laura;Kuse, Nozomi;Nicoli, Francesco
近年来，Toll样受体9（TLR 9）激动剂作为诱导适应性免疫应答的潜在佐剂获得了关注。尽管如此，仍不清楚这些配体在多大程度上可以促进产生抗原特异性效应和/或记忆CD 8（+）T细胞群的引发事件。我们使用已建立的体外模型在各种佐剂（包括CpG ODN 2006，一种合成的寡核苷酸TLR 9配体（TLR 9 L））的存在下引发来自人外周血单核细胞的幼稚前体。出乎意料的是，我们发现TLR 9 L诱导了次优的炎性环境，并且与激活其他模式识别受体（PRR）的ssRNA 40或2 ' 3 ' -cGAMP相比，TLR 9 L无效地促进了初始CD 8（+）T细胞的抗原驱动的扩增和功能成熟。TLR 9 L还抑制2 ' 3 ' -cGAMP的引发功效。总的来说，这些结果表明，与通过离散PRR起作用的佐剂相比，TLR 9 L不太可能是从头CD 8（+）T细胞应答的最佳诱导的良好候选物。
Toll-like receptor 9 (TLR9) agonists have gained traction in recent years as potential adjuvants for the induction of adaptive immune responses. It has nonetheless remained unclear to what extent such ligands can facilitate the priming events that generate antigen-specific effector and/or memory CD8(+) T-cell populations. We used an established in vitro model to prime naive precursors from human peripheral blood mononuclear cells in the presence of various adjuvants, including CpG ODN 2006, a synthetic oligonucleotide TLR9 ligand (TLR9L). Unexpectedly, we found that TLR9L induced a suboptimal inflammatory milieu and promoted the antigen-driven expansion and functional maturation of naive CD8(+) T cells ineffectively compared with either ssRNA40 or 2 ' 3 ' -cGAMP, which activate other pattern recognition receptors (PRRs). TLR9L also inhibited the priming efficacy of 2 ' 3 ' -cGAMP. Collectively, these results suggest that TLR9L is unlikely to be a good candidate for the optimal induction of de novo CD8(+) T-cell responses, in contrast to adjuvants that operate via discrete PRRs.