Polyriboinosinic polyribocytidylic acid [poly(I:C)]/TLR3 signaling allows class I processing of exogenous protein and induction of HIV-specific CD8+ cytotoxic T lymphocytes
Polyriboinosinic polyribocytidylic acid [poly(I:C)]/TLR3 signaling allows class I processing of exogenous protein and induction of HIV-specific CD8+ cytotoxic T lymphocytes
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DOI：
10.1093/intimm/dxh025
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发表时间：
2004-01-01
影响因子：
4.4
通讯作者：
Takahashi, H
中科院分区：
文献类型：
--
作者：
Fujimoto, C;Nakagawa, Y;Takahashi, H
在病毒感染的情况下，各种病毒蛋白质和遗传成分在体内传播。前者的病毒蛋白可以被未成熟的树突状细胞（DC）捕获，后者的遗传成分可以通过特异性Toll样受体（TLR）刺激抗原负载DC成熟，从而建立病毒特异性细胞免疫;特别是控制细胞内病毒体的细胞毒性T淋巴细胞（CTL）。多聚核糖肌苷酸多聚核糖胞苷酸[poly（I：C）]可能反映了多种病毒在复制过程中的天然遗传产物，最近已被鉴定为TLR 3的关键刺激物之一。基于这些观察结果，我们推测poly（I：C）对TLR 3的刺激可能驱动获得性/适应性免疫向细胞臂的方向发展。事实上，当用纯化的重组HIV-1包膜gp 120或流感血凝素（HA）蛋白与poly（I：C）一起免疫BALB/c小鼠时，表位特异性CD 8（+）I类MHC分子限制性CTL从体内初始CD 8（+）T细胞中引发。相反，当用TLR 4的刺激物脂多糖免疫相同的蛋白质时，特异性CTL根本不被引发。此外，我们在这里表明，未成熟的DC可以提出处理的抗原从捕获的纯化蛋白与I类MHC分子在聚（I：C）的存在下，但不是LPS。这些结果表明，我们能够使用适当的刺激操纵获得性/适应性效应免疫应答的方向，并且本文中的发现将提供一种新的治疗策略，其使用poly（I：C）施用以在体内用纯化的病毒蛋白引发抗原特异性CD 8（+）CTL。
In the case of viral infection, various viral proteins and genetic components are disseminated in the body. The former viral proteins may be captured by immature dendritic cells (DC) and the latter genetic components may stimulate the antigen-loading DC to maturate via specific Toll-like receptors (TLR), leading to the establishment of virus-specific cellular immunity; in particular, cytotoxic T lymphocytes (CTL) that control intracellular virions. Polyriboinosinic polyribocytidylic acid [poly(I:C)], which might reflect a natural genetic product from a variety of viruses during replication, has recently been identified as one of the critical stimuli for TLR3. Based on these observations, we speculated that stimulation of TLR3 with poly(I:C) might drive the direction of acquired/adaptive immunity to the cellular arm. Indeed, when BALB/c mice were immunized with purified recombinant HIV-1 envelope gp120 or influenza hemagglutinin (HA) protein together with poly(I:C), epitope-specific CD8(+) class I MHC molecule-restricted CTL were primed from naive CD8(+) T cells in vivo. In contrast, when the same proteins were immunized with lipopolysaccharide, a stimulant of TLR4, specific CTL were not primed at all. Moreover, we show here that immature DC could present processed antigen from captured purified protein in association with class I MHC molecules in the presence of poly(I:C), but not of LPS. These results indicate that we are able to manipulate the direction of acquired/adaptive effector immune responses using an appropriate stimuli and the findings presented in this paper will offer a new therapeutic strategy using poly(I:C) administration for priming antigen-specific CD8(+) CTL with purified viral protein in vivo.