Institute of Immunology, Hannover Medical School, Hannover, Germany.
Department of Internal Medicine I, University of Ulm, Ulm, Germany.
Mucosal Immunol. 2014 Jul;7(4):892-904. doi: 10.1038/mi.2013.105. Epub 2013 Dec 18.
Lymphoid organ hypertrophy is a hallmark of localized infection. During the inflammatory response, massive changes in lymphocyte recirculation and turnover boost lymphoid organ cellularity. Intriguingly, the exact nature of these changes remains undefined to date. Here, we report that hypertrophy of Salmonella-infected Peyer's patches (PPs) ensues from a global "shutdown" of lymphocyte egress, which traps recirculating lymphocytes in PPs. Surprisingly, infection-induced lymphocyte sequestration did not require previously proposed mediators of lymphoid organ shutdown including type I interferon receptor and CD69. In contrast, following T-cell receptor-mediated priming, CD69 was essential to selectively block CD4(+) effector T-cell egress. Our findings segregate two distinct lymphocyte sequestration mechanisms, which differentially rely on intrinsic modulation of lymphocyte egress capacity and inflammation-induced changes in the lymphoid organ environment.
淋巴器官肥大是局部感染的一个标志。在炎症反应过程中,淋巴细胞再循环和更新的大量变化会增加淋巴器官的细胞数量。有趣的是,这些变化的确切性质至今仍未确定。在这里,我们报告称,沙门氏菌感染的派尔氏集合淋巴结(PP)的肥大是由于淋巴细胞流出的全面“关闭”所致,这会将循环中的淋巴细胞困在 PP 中。令人惊讶的是,感染诱导的淋巴细胞隔离并不需要先前提出的淋巴器官关闭的介质,包括 I 型干扰素受体和 CD69。相比之下,在 T 细胞受体介导的启动后,CD69 对于选择性地阻止 CD4+效应 T 细胞的流出是必不可少的。我们的研究结果将两种不同的淋巴细胞隔离机制分开,这两种机制分别依赖于淋巴细胞流出能力的内在调节和炎症诱导的淋巴器官环境变化。