Regulation of T cell priming by lymphoid stroma.

Regulation of T cell priming by lymphoid stroma.
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通过淋巴样基质调节T细胞启动。

DOI:
10.1371/journal.pone.0026138
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Krummel MF
Krummel MF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Khan O;Headley M;Gerard A;Wei W;Liu L;Krummel MF

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免疫T细胞通过与淋巴结(LN)中的树突状细胞(DC)相互作用而引发,这是生产性适应性免疫应答的早期事件之一,发生在淋巴基质细胞的支架上,淋巴基质细胞在很大程度上被视为支持细胞或趋化因子和稳态生长因子的来源。在这里,我们表明,小鼠成纤维网状细胞(FRC),分离自LN的B6小鼠,发挥更直接的作用,通过感应和调节T细胞的活化,通过上调诱导型一氧化氮合酶(iNOS),以响应早期T细胞IFNγ的产生。基质iNOS,它只在非常接近的功能,减弱炎症DC免疫的反应,但不其他引发方案,并优先影响Th 1细胞,而不是Th 2。由此产生的一氧化氮不影响T细胞-DC偶联或初始钙信号传导,但限制同型T细胞聚集、细胞周期进展和增殖。因此,基质反馈抑制提供了T细胞应答的基础衰减,特别是以强局部炎症线索为特征的那些。
The priming of immune T cells by their interaction with dendritic cells (DCs) in lymph nodes (LN), one of the early events in productive adaptive immune responses, occurs on a scaffold of lymphoid stromal cells, which have largely been seen as support cells or sources of chemokines and homeostatic growth factors. Here we show that murine fibroblastic reticular cells (FRCs), isolated from LN of B6 mice, play a more direct role in the immune response by sensing and modulating T cell activation through their upregulation of inducible nitric oxide synthase (iNOS) in response to early T cell IFNγ production. Stromal iNOS, which only functions in very close proximity, attenuates responses to inflammatory DC immunization but not to other priming regimens and preferentially affects Th1 cells rather than Th2. The resultant nitric oxide production does not affect T cell-DC coupling or initial calcium signaling, but restricts homotypic T cell clustering, cell cycle progression, and proliferation. Stromal feedback inhibition thus provides basal attenuation of T cell responses, particularly those characterized by strong local inflammatory cues.
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