The TLR3 agonist poly(I:C) targets CD8+ T cells and augments their antigen-specific responses upon their adoptive transfer into naïve recipient mice.
The TLR3 agonist poly(I:C) targets CD8+ T cells and augments their antigen-specific responses upon their adoptive transfer into naïve recipient mice.
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DOI：
10.1016/j.vaccine.2008.11.013
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发表时间：
2009-01-22
期刊：
影响因子：
5.5
通讯作者：
Cole DJ
中科院分区：
文献类型：
--
作者：
Salem ML;Diaz-Montero CM;El-Naggar SA;Chen Y;Moussa O;Cole DJ
我们最近报道了toll样受体3 （TLR3）激动剂poly（I:C）通过快速诱导先天介质，包括NK细胞、巨噬细胞、树突状细胞（DCs）和炎症细胞因子，诱导疫苗接种后CD8+ T细胞反应的佐剂效应。然而，这种TLR3激动剂是否直接靶向CD8+ T细胞还需要仔细研究。在本研究中，我们发现体外dc疫苗接种后CD8+ T细胞的最佳应答需要在体外dc和受体宿主中触发TLR3信号通路，这表明其他细胞类型也有作用。Real-time PCR分析显示，TLRs （TLR1-TLR13）在C57BL/6和BALB/c小鼠纯化（>99%纯）CD4+和CD8+ T细胞中表达，其表达量依赖于菌株和细胞类型。在体外，用poly（I:C）处理这些纯化的T细胞可以调节包括TLR3在内的tlr的表达。此外，肉豆蔻酸酯phorbol acetate和MHC I类肽脉冲脾细胞分别对CD8+ T细胞进行非特异性和抗原特异性刺激，可调节纯化CD4+和CD8+ T细胞中TLR的表达。重要的是，在体外用poly（I:C）短暂调节纯化的naïve TCR转基因OT-1 (CD8+) T细胞诱导这些细胞在没有抗原刺激的情况下活化。有趣的是，当这些体外poly（I:C）条件的OT-1细胞被过过性地转移到naïve受体中，然后接种肽疫苗时，它们表现出比naïve对应体更好的扩增和激活。这些结果表明CD8+ T细胞可以通过触发它们的TLR3而被激活。此外，这些数据支持tlr直接参与适应性免疫反应的概念。
We have recently reported that the toll-like receptor 3 (TLR3) agonist poly(I:C) induces adjuvant effects to post vaccination CD8+ T cells responses through rapid induction of innate mediators, including NK cells, macrophages, dendritic cells (DCs), and inflammatory cytokines. However, whether this TLR3 agonist directly targets CD8+ T cells needs to be carefully investigated. In this study, we found that optimal post vaccination CD8+ T cell responses to ex vivo DC-based vaccination requires triggering of TLR3 signaling pathway in DCs in vitro as well as in the recipient host, indicating a role for other cell types. Real-time PCR analysis revealed that TLRs (TLR1–TLR13) are expressed in purified (>99% pure) CD4+ and CD8+ T cells from C57BL/6 and BALB/c mice, where the magnitude of the expression was strain and cell type dependent. In vitro, treatment of these purified T cells with poly(I:C) modulated the expression of TLRs including TLR3. Furthermore, non-specific and antigen-specific stimulation of CD8+ T cells by phorbol myristate acetate and MHC class I peptide-pulsed splenocytes, respectively, modulated TLR expression in purified CD4+ and CD8+ T cells. Importantly, brief conditioning of purified naïve TCR transgenic OT-1 (CD8+) T cells in vitro with poly(I:C) induced activation of these cells in absence of antigen stimulation. Interestingly, when these in vitro poly(I:C)-conditioned OT-1 cells were adoptively transferred into naïve recipient followed by peptide vaccination, they showed superior expansion and activation to their naïve counterparts. These results suggest that CD8+ T cells can be activated by triggering their TLR3. Furthermore, the data support the notion of direct involvement of TLRs in adaptive immune responses.
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影响因子：
64.8
作者：
Horng, T;Barton, GM;Medzhitov, R
通讯作者：
Medzhitov, R
DOI：
10.1073/pnas.1934678100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Honda, K;Sakaguchi, S;Taniguchi, T
通讯作者：
Taniguchi, T
影响因子：
4.4
作者：
Loré, K;Betts, MR;Koup, RA
通讯作者：
Koup, RA
影响因子：
1.8
作者：
Ignacio, G;Nordone, S;Dean, GA
通讯作者：
Dean, GA
DOI：
10.1084/jem.20050821
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolumam GA;Thomas S;Thompson LJ;Sprent J;Murali-Krishna K
通讯作者：
Murali-Krishna K