外周定位和局部 CXCL9 趋化因子介导的导向协调淋巴结中快速的记忆性 CD8+T 细胞应答。
Peripheral prepositioning and local CXCL9 chemokine-mediated guidance orchestrate rapid memory CD8+ T cell responses in the lymph node.
机构信息
Lymphocyte Biology Section, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Immunity. 2013 Mar 21;38(3):502-13. doi: 10.1016/j.immuni.2012.11.012. Epub 2013 Jan 24.
After an infection, the immune system generates long-lived memory lymphocytes whose increased frequency and altered state of differentiation enhance host defense against reinfection. Recently, the spatial distribution of memory cells was found to contribute to their protective function. Effector memory CD8+ T cells reside in peripheral tissue sites of initial pathogen encounter, in apparent anticipation of reinfection. Here we show that within lymph nodes (LNs), memory CD8+ T cells were concentrated near peripheral entry portals of lymph-borne pathogens, promoting rapid engagement of infected sentinel macrophages. A feed-forward CXCL9-dependent circuit provided additional chemotactic cues that further increase local memory cell density. Memory CD8+ T cells also produced effector responses to local cytokine triggers, but their dynamic behavior differed from that seen after antigen recognition. These data reveal the distinct localization and dynamic behavior of naive versus memory T cells within LNs and how these differences contribute to host defense.
感染后,免疫系统会产生长寿记忆性淋巴细胞,其频率增加和分化状态改变增强了宿主对再感染的防御能力。最近,人们发现记忆细胞的空间分布有助于其保护功能。效应记忆性 CD8+T 细胞存在于初始病原体入侵的外周组织部位,显然是为了再次感染做准备。在这里,我们发现,在淋巴结 (LNs) 中,记忆性 CD8+T 细胞集中在淋巴管病原体进入的外周入口附近,促进了感染的哨兵巨噬细胞的快速参与。一个正反馈的 CXCL9 依赖的循环提供了额外的趋化线索,进一步增加了局部记忆细胞的密度。记忆性 CD8+T 细胞也对局部细胞因子触发产生效应反应,但它们的动态行为与抗原识别后观察到的不同。这些数据揭示了在 LNs 中,幼稚 T 细胞与记忆 T 细胞的不同定位和动态行为,以及这些差异如何有助于宿主防御。