IFN-γ Regulates CD8+ Memory T Cell Differentiation and Survival in Response to Weak, but Not Strong, TCR Signals
IFN-γ Regulates CD8+ Memory T Cell Differentiation and Survival in Response to Weak, but Not Strong, TCR Signals
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DOI：
10.4049/jimmunol.1402058
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发表时间：
2015-01-15
影响因子：
4.4
通讯作者：
Schueler, Thomas
中科院分区：
文献类型：
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作者：
Stoycheva, Diana;Deiser, Katrin;Schueler, Thomas
作为对原代银接触的反应，小鼠CD8(+) T细胞进行克隆扩增并分化为效应T细胞。在病原体清除后，大多数效应T细胞死亡，只有少数记忆T细胞前体（T- mps）存活，形成一个长寿命记忆T细胞（T- ms）池。虽然高亲和力和低亲和力的CD8(+) T细胞克隆被招募到主要应答中，但T- m池主要由高亲和力的克隆组成。目前尚不清楚高亲和力克隆和/或细胞内在过程的更有效扩展是否将低亲和力T细胞排除在T- m池之外。在这篇文章中，我们发现CD8(+) T细胞中缺乏ifn - γ R信号可以促进T- m的形成，以响应弱而不是强的TCR激动剂。ifn - γ敏感的T-Ms积累与哺乳动物雷帕霉素激活靶点的降低和长寿命CD62L(hi)Bcl-2(hi) Eomes(hi) T-MPs的积累相关。重组哺乳动物雷帕霉素靶点或ifn - γ R信号足以阻断这一过程。因此，我们的数据表明，ifn - γ R信号主动阻断对弱TCR激动剂反应的T- mps的形成，从而促进高亲和力T细胞的积累，最终主导T- m池。
In response to primary Ag contact, naive mouse CD8(+) T cells undergo clonal expansion and differentiate into effector T cells. After pathogen clearance, most effector T cells die, and only a small number of memory T cell precursors (T-MPs) survive to form a pool of long-lived memory T cells (T-Ms). Although high-and low-affinity CD8(+) T cell clones are recruited into the primary response, the T-M pool consists mainly of high-affinity clones. It remains unclear whether the more efficient expansion of high-affinity clones and/or cell-intrinsic processes exclude low-affinity T cells from the T-M pool. In this article, we show that the lack of IFN-gamma R signaling in CD8(+) T cells promotes T-M formation in response to weak, but not strong, TCR agonists. The IFN-gamma-sensitive accumulation of T-Ms correlates with reduced mammalian target of rapamycin activation and the accumulation of long-lived CD62L(hi)Bcl-2(hi) Eomes(hi) T-MPs. Reconstitution of mammalian target of rapamycin or IFN-gamma R signaling is sufficient to block this process. Hence, our data suggest that IFN-gamma R signaling actively blocks the formation of T-MPs responding to weak TCR agonists, thereby promoting the accumulation of high-affinity T cells finally dominating the T-M pool.