IL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death.

IL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death.
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DOI:
10.1038/ni.2494
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发表时间:
2013-02
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
文献类型:
--
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维持幼稚的CD8T细胞对于终生免疫功能是必要的,但由于未知的原因,需要白介素7(IL-7)和T细胞受体(TCR)信号。我们现在报道,初治的CD8T细胞需要间歇性的IL-7信号,而不是连续的,因为长时间的IL-7信号诱导初治的CD8T细胞增殖,产生干扰素-γ(干扰素-γ),并经历干扰素-γ触发的细胞死亡。动态平衡的TCR参与干扰IL-7信号,从而支持CD8 T细胞的存活和静止。然而,对自身配体TCR亲和力不足的CD8T细胞会收到长时间的IL-7信号,并在动态平衡期间死亡。这项研究确定了体内CD8T细胞稳态的基础是通过稳态TCR参与调节IL-7信号持续时间。
Maintenance of naive CD8 T cells is necessary for lifelong immunocompetence but for unknown reasons requires both interleukin-7 (IL-7) and T cell receptor (TCR) signaling. We now report that naive CD8 T cells require IL-7 signaling to be intermittent, not continuous, because prolonged IL-7 signaling induces naive CD8 T cells to proliferate, produce interferon-γ (IFN-γ), and undergo IFN-γ-triggered cell death. Homeostatic TCR engagements interrupt IL-7 signaling and thereby support CD8 T cell survival and quiescence. However, CD8 T cells with insufficient TCR affinity for self-ligands receive prolonged IL-7 signaling and die during homeostasis. This study identifies the regulation of IL-7 signaling duration by homeostatic TCR engagements as the basis for in vivo CD8 T cell homeostasis.
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发表时间: 1999-08-01
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