Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN.
Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN.
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DOI：
10.1084/jem.20031591
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发表时间：
2004-03-15
期刊：
影响因子：
--
通讯作者：
Kedl RM
中科院分区：
文献类型：
--
作者：
Ahonen CL;Doxsee CL;McGurran SM;Riter TR;Wade WF;Barth RJ;Vasilakos JP;Noelle RJ;Kedl RM
Toll样受体在先天免疫的激活中是重要的，并且CD 40是许多T和B细胞应答的关键分子。尽管任一途径的激动剂已被用作疫苗佐剂，但我们表明Toll样受体（TLR）7和CD 40激动剂的组合协同作用以刺激比单独使用任一激动剂高10-20倍的CD 8 + T细胞应答。由组合CD 40/TLR 7处理引发的抗原特异性CD 8 + T细胞表现出裂解活性和干扰素（IFN）γ产生以及对抗原攻击的增强的次级应答。TLR 2/6、3、4和9的激动剂也与CD 40刺激协同作用，表明与CD 40途径的协同作用通常是TLR衍生的刺激的性质。由CD 40/TLR 7触发诱导的CD 8 + T细胞扩增不依赖于CD 4 + T细胞、IFNγ和IL-12，但依赖于B7介导的共刺激，并且令人惊讶地依赖于I型IFN。这些研究为同时使用TLR和CD 40激动剂作为基本佐剂来优化旨在引起保护性或治疗性免疫的疫苗提供了合理的基础。
Toll-like receptors are important in the activation of innate immunity, and CD40 is a molecule critical for many T and B cell responses. Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10–20-fold greater than the use of either agonist alone. Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)γ production and an enhanced secondary response to antigenic challenge. Agonists for TLRs 2/6, 3, 4, and 9 also synergized with CD40 stimulation, demonstrating that synergy with the CD40 pathway is a property of TLR-derived stimuli in general. The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNγ, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN. These studies provide the rational basis for the use of TLR and CD40 agonists together as essential adjuvants to optimize vaccines designed to elicit protective or therapeutic immunity.
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