CpG and Interleukin-15 Synergize to Enhance IFN-γ Production by Activated CD8+ T Cells
CpG and Interleukin-15 Synergize to Enhance IFN-γ Production by Activated CD8+ T Cells
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DOI：
10.1155/2013/924023
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Smeltz, Ronald B.
中科院分区：
文献类型：
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作者：
Cobb, Dustin;Guo, Siqi;Smeltz, Ronald B.
白细胞介素-15（IL-15）调节记忆性CD 8（+）T细胞的发育和维持。巧合的是，我们以前报道IL-15可以增强CD 8（+）T细胞对IL-12的反应，IL-12是一种促炎细胞因子，是效应CD 8（+）T细胞最佳引发所必需的。为了扩大这些发现的生理相关性，我们测试了IL-15增强T细胞对细菌CpG应答的能力。预期，CpG增强了用抗CD 3多克隆激活的CD 8（+）T细胞产生IFN-γ。然而，将IL-15添加到CpG刺激的培养物中导致IFN-γ产生的显著增加。CpG和IL-15的作用在从感染寄生虫克氏锥虫（Trypanosoma cruzi）的小鼠中回收的CD 8（+）T细胞中也很明显。cruzi）并用抗原重新刺激。观察到的CpG和IL-15之间的协同作用以IL-12依赖的方式发生，这种作用甚至可以在活化的CD 8（+）T细胞和CD 4（+）CD 25（+）调节性T细胞的共培养物中得到证实。尽管IFN-γ对于CpG诱导的IL-12不是必需的，但CpG和IL-15作用于CD 8（+）T细胞的能力需要IFN-γ诱导的转录因子T-bet的表达。这些数据对疫苗的开发和疗法的设计具有重要意义，以增强CD 8（+）T细胞对感染因子和肿瘤的反应。
Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8(+) T cells. Paradoxically, we previously reported that IL-15 could enhance CD8(+) T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8(+) T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-gamma by CD8(+) T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-gamma production. The effect of CpG and IL-15 was also evident with CD8(+) T cells recovered from mice infected with the parasite Trypanosoma cruzi (T. cruzi) and restimulated with antigen. The observed synergy between CpG and IL-15 occurred in an IL-12-dependent manner, and this effect could even be demonstrated in cocultures of activated CD8(+) T cells and CD4(+)CD25(+) regulatory T cells. Although IFN-gamma was not essential for CpG-induced IL-12, the ability of CpG and IL-15 to act on CD8(+) T cells required expression of the IFN-gamma-inducible transcription factor T-bet. These data have important implications for development of vaccines and design of therapies to boost CD8(+) T-cell responses to infectious agents and tumors.