Department of Pathology, University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2011;6(11):e26138. doi: 10.1371/journal.pone.0026138. Epub 2011 Nov 14.
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.
免疫 T 细胞与淋巴结（LN）中的树突状细胞（DC）相互作用而被激活，这是适应性免疫反应的早期事件之一，其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，从 B6 小鼠 LN 中分离出的鼠成纤维网状细胞（FRC）通过感应和调节 T 细胞激活，在免疫反应中发挥更直接的作用，其方式是通过对早期 T 细胞 IFNγ产生的反应而上调诱导型一氧化氮合酶（iNOS）。仅在非常接近的情况下起作用的基质 iNOS 会减弱对炎症性 DC 免疫接种的反应，但不会减弱对其他启动方案的反应，并且优先影响 Th1 细胞而不是 Th2 细胞。由此产生的一氧化氮产生不会影响 T 细胞-DC 偶联或初始钙信号，但会限制同质 T 细胞聚集、细胞周期进程和增殖。因此，基质反馈抑制提供了 T 细胞反应的基础衰减，特别是那些以强烈的局部炎症信号为特征的反应。
