IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17.
IL-12 produced by dendritic cells augments CD8+ T cell activation through the production of the chemokines CCL1 and CCL17.
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DOI：
10.4049/jimmunol.181.12.8576
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发表时间：
2008-12-15
期刊：
影响因子：
--
通讯作者：
Hiltbold EM
中科院分区：
文献类型：
--
作者：
Henry CJ;Ornelles DA;Mitchell LM;Brzoza-Lewis KL;Hiltbold EM
白细胞介素-12 （IL-12）家族成员是先天免疫和适应性免疫之间的重要纽带。IL-12通过增加IFN-γ的产生来驱动Th1反应，IFN-γ是清除细胞内病原体的关键。白细胞介素-23 （IL-23）促进产生IL-17的CD4+ T细胞的发育，参与控制细胞外病原体和诱导自身免疫。然而，最近的研究表明，这些细胞因子可以调节淋巴细胞迁移和细胞相互作用。因此，我们试图通过研究IL-12和IL-23在单核增生李斯特菌（Lm）感染树突状细胞（DC）启动过程中影响干扰素γ (IFN-γ)产生和细胞相互作用动力学的能力，确定IL-12和IL-23在naïve CD8+ T细胞激活中的个体作用。我们发现IL-12是影响CD8+ T细胞产生IFN-γ水平的主要细胞因子，而IL-23对这一反应几乎没有影响。此外，我们观察到IL-12促进CD8+ T细胞与DC之间持续时间更长的结合事件。这种同源相互作用时间的增加与野生型DC趋化因子CCL1和CCL17的产生相关，而与IL-12缺陷DC无关。这两种趋化因子的中和减少了相互作用时间和IFN-γ的产生，证明了它们在启动naïve CD8+ T细胞中的重要性。我们的研究证明了一种新的机制，IL-12通过促进趋化因子的产生来增强naïve CD8+ T细胞的激活，从而在启动过程中促进更稳定的同源相互作用。
Interleukin-12 (IL-12) family members are an important link between innate and adaptive immunity. IL-12 drives Th1 responses by augmenting IFN-γ production, which is key for clearance of intracellular pathogens. Interleukin-23 (IL-23) promotes the development of IL-17 producing CD4+ T cells that participate in the control of extracellular pathogens and the induction of autoimmunity. However, recent studies have shown that these cytokines can modulate lymphocyte migration and cellular interactions. Therefore, we sought to determine the individual roles of IL-12 and IL-23 in naïve CD8+ T cell activation by addressing their ability to influence interferon gamma (IFN-γ) production and cellular interaction dynamics during priming by Listeria monocytogenes (Lm)-infected dendritic cells (DC). We found that IL-12 was the major cytokine influencing the level of IFN-γ production by CD8+ T cells while IL-23 had little effect on this response. In addition, we observed that IL-12 promoted longer duration conjugation events between CD8+ T cells and DC. This enhanced cognate interaction time correlated increased production of the chemokines CCL1 and CCL17 by wild-type but not IL-12 deficient DC. Neutralization of both chemokines resulted in reduced interaction time and IFN-γ production demonstrating their importance in priming naïve CD8+ T cells. Our study demonstrates a novel mechanism through which IL-12 augments naïve CD8+ T cell activation by facilitating chemokine production thus promoting more stable cognate interactions during priming.
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DOI：
10.1084/jem.20021910
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Curtsinger JM;Lins DC;Mescher MF
通讯作者：
Mescher MF
影响因子：
64.5
作者：
Geijtenbeek, TBH;Torensma, R;Figdor, CG
通讯作者：
Figdor, CG
影响因子：
4.4
作者：
Gombert, M;Dieu-Nosjean, MC;Homey, B
通讯作者：
Homey, B
影响因子：
4.4
作者：
Chang, J;Cho, JH;Sung, YC
通讯作者：
Sung, YC
影响因子：
82.9
作者：
Badovinac, VP;Messingham, KAN;Harty, JT
通讯作者：
Harty, JT