Zhang Minghui, Tang Hua, Guo Zhenhong, An Huazhang, Zhu Xuejun, Song Wengang, Guo Jun, Huang Xin, Chen Taoyong, Wang Jianli, Cao Xuetao
The Institute of Immunology, Second Military Medical University, Shanghai, China.
Nat Immunol. 2004 Nov;5(11):1124-33. doi: 10.1038/ni1130. Epub 2004 Oct 10.
The fates of dendritic cells (DCs) after antigen presentation have been studied extensively, but the influence of lymphoid microenvironments on DCs is mostly unknown. Here, using splenic stromal cells to mimic the immune microenvironment, we show that contact with stromal cells promoted mature DCs to proliferate in a fibronectin-dependent way and that both stromal cell contact and stromal cell-derived transforming growth factor-beta induced their differentiation into a new regulatory DC subset. We have identified an in vivo counterpart in the spleen with similar phenotype and functions. These differentiated DCs secreted nitric oxide, which mediated the suppression of T cell proliferation in response to antigen presentation by mature DCs. Thus, our findings identify an important mechanism by which the microenvironment regulates immune responses.
抗原呈递后树突状细胞（DCs）的命运已得到广泛研究，但淋巴微环境对DCs的影响大多未知。在这里，我们利用脾基质细胞模拟免疫微环境，发现与基质细胞的接触促进成熟DCs以纤连蛋白依赖的方式增殖，并且基质细胞接触和基质细胞衍生的转化生长因子-β均诱导它们分化为一个新的调节性DC亚群。我们在脾脏中鉴定出了具有相似表型和功能的体内对应物。这些分化的DCs分泌一氧化氮，其介导对成熟DCs抗原呈递的T细胞增殖抑制。因此，我们的发现确定了微环境调节免疫反应的重要机制。
