Regulation of innate CD8+ T-cell activation mediated by cytokines
Regulation of innate CD8+ T-cell activation mediated by cytokines
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DOI：
10.1073/pnas.1203543109
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发表时间：
2012-06-19
影响因子：
11.1
通讯作者：
Slifka, Mark K.
中科院分区：
文献类型：
--
作者：
Freeman, Bailey E.;Hammarlund, Erika;Slifka, Mark K.
病毒特异性CD 8（+）T细胞通过以TCR非依赖性方式响应一系列显著的细胞因子而发展出以“先天”能力发挥功能的能力。虽然几种细胞因子如IL-12和IL-18已被确定为CD 8（+）T细胞活化的关键调节因子，但其他细胞因子的作用以及它们相互作用的方式仍不清楚。在这里，我们使用了一种无偏见的系统方法来检查1，849种细胞因子组合对病毒特异性CD 8（+）T细胞活化的影响。本研究鉴定了几种意想不到的细胞因子组合，其协同诱导抗原非依赖性IFN γ产生和CD 8（+）T细胞的CD 69上调，除了表现出差异调节功能的细胞因子之外，还具有增强或抑制T细胞IFN γ产生的能力，这取决于存在哪种细胞因子伴侣。这些发现强调了细胞因子相互作用的复杂性，同时也为控制病毒特异性CD 8（+）T细胞功能的多方面调控网络提供了见解。
Virus-specific CD8(+) T cells develop the ability to function in an "innate" capacity by responding to a remarkable array of cytokines in a TCR-independent manner. Although several cytokines such as IL-12 and IL-18 have been identified as key regulators of CD8(+) T-cell activation, the role of other cytokines and the ways in which they interact with each other remain unclear. Here, we have used an unbiased, systematic approach to examine the effects of 1,849 cytokine combinations on virus-specific CD8(+) T-cell activation. This study identifies several unexpected cytokine combinations that synergize to induce antigen-independent IFN gamma production and CD69 up-regulation by CD8(+) T cells in addition to cytokines that exhibit differential regulatory functions, with the ability to either enhance or inhibit T-cell IFN gamma production, depending on which cytokine partner is present. These findings underscore the complexity of cytokine interactions while also providing insight into the multifaceted regulatory network controlling virus-specific CD8(+) T-cell functions.