T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection
T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection
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DOI：
10.1073/pnas.1516485113
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发表时间：
2016-02-23
影响因子：
11.1
通讯作者：
Khanna, Kamal M.
中科院分区：
文献类型：
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作者：
Benechet, Alexandre P.;Menon, Manisha;Khanna, Kamal M.
病毒清除需要效应T细胞从引流淋巴结（dLN）流出。人们对感染后调节效应T细胞从dLN排出的复杂过程的机制知之甚少。在这里，我们可视化内源性病原体特异性效应T细胞迁移内，并从，dLN。我们使用了一种诱导型小鼠模型，在内源性效应T细胞中特异性地具有暂时中断的鞘氨醇-1-磷酸受体-1（S1 PR 1）基因。感染后早期，WT和S1 PR 1（-/-）效应T细胞仅定位于副皮质内。这种由CD 8 T细胞在副皮质中的定位之后，WT和S1 PR 1（-/-）T细胞都向邻近皮质和髓质淋巴窦的位置的结内迁移，在那里T细胞表现出强烈的探测行为。然而，与WT相反，S1 PR 1（-/-）效应T细胞未能进入鼻窦。我们证明，即使当LN滞留信号，如CC趋化因子受体7（CCR 7）下调，T细胞固有的S1 PR 1是主调节效应T细胞从dLN移民。
Viral clearance requires effector T-cell egress from the draining lymph node (dLN). The mechanisms that regulate the complex process of effector T-cell egress from the dLN after infection are poorly understood. Here, we visualized endogenous pathogen-specific effector T-cell migration within, and from, the dLN. We used an inducible mouse model with a temporally disrupted sphingosine-1-phosphate receptor-1 (S1PR1) gene specifically in endogenous effector T cells. Early after infection, WT and S1PR1(-/-) effector T cells localized exclusively within the paracortex. This localization in the paracortex by CD8 T cells was followed by intranodal migration by both WT and S1PR1(-/-) T cells to positions adjacent to both cortical and medullary lymphatic sinuses where the T cells exhibited intense probing behavior. However, in contrast to WT, S1PR1(-/-) effector T cells failed to enter the sinuses. We demonstrate that, even when LN retention signals such as CC chemokine receptor 7 (CCR7) are down-regulated, T cell intrinsic S1PR1 is the master regulator of effector T-cell emigration from the dLN.