IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo.
IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo.
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DOI：
10.1084/jem.20130901
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发表时间：
2014-01-13
期刊：
影响因子：
--
通讯作者：
Harty JT
中科院分区：
文献类型：
--
作者：
Starbeck-Miller GR;Xue HH;Harty JT
信号3细胞因子白细胞介素-12和I型干扰素通过延长体内CD 25的表达来维持CD 8 T细胞分裂。TCR连接和共刺激诱导细胞分裂;然而，效应CD 8 T细胞的最佳积累需要通过信号3细胞因子如IL-12或I型IFN的直接炎症信号传导。尽管体外研究表明IL-12/I型IFN可增强T细胞存活或早期增殖，但体内CD 8 T细胞最佳积累的机制尚不清楚。特别是，目前还不清楚不同的信号3细胞因子是否通过相同的机制优化效应CD 8 T细胞积累，以及这些在感染后早期瞬时产生的炎性细胞因子如何影响多天后免疫应答高峰时的T细胞积累。在这里，我们表明，瞬时暴露的CD 8 T细胞IL-12或I型IFN不促进生存或赋予体内早期增殖的优势，而是维持表面表达的CD 25，高亲和力的IL-2受体。这通过PI 3 K途径的激活和细胞周期进展基因的正调节因子FoxM 1的表达，抑制了CD 8 T细胞响应于基础IL-2的分裂。因此，信号3细胞因子使用共同途径通过维持分裂而不是存活的细胞因子信号的时间协调序列来优化效应CD 8 T细胞积累。
The signal 3 cytokines interleukin-12 and type I interferon sustain CD8 T cell division by prolonging expression of CD25 in vivo. TCR ligation and co-stimulation induce cellular division; however, optimal accumulation of effector CD8 T cells requires direct inflammatory signaling by signal 3 cytokines, such as IL-12 or type I IFNs. Although in vitro studies suggest that IL-12/type I IFN may enhance T cell survival or early proliferation, the mechanisms underlying optimal accumulation of CD8 T cells in vivo are unknown. In particular, it is unclear if disparate signal 3 cytokines optimize effector CD8 T cell accumulation by the same mechanism and how these inflammatory cytokines, which are transiently produced early after infection, affect T cell accumulation many days later at the peak of the immune response. Here, we show that transient exposure of CD8 T cells to IL-12 or type I IFN does not promote survival or confer an early proliferative advantage in vivo, but rather sustains surface expression of CD25, the high-affinity IL-2 receptor. This prolongs division of CD8 T cells in response to basal IL-2, through activation of the PI3K pathway and expression of FoxM1, a positive regulator of cell cycle progression genes. Thus, signal 3 cytokines use a common pathway to optimize effector CD8 T cell accumulation through a temporally orchestrated sequence of cytokine signals that sustain division rather than survival.
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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：
--
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