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Memory CD8+ T cells mediate early pathogen-specific protection via localized delivery of chemokines and IFNγ to clusters of monocytes
Science Advances ( IF 11.7 ) Pub Date : 2021-09-01 , DOI: 10.1126/sciadv.abf9975
Marie Boutet 1 , Zachary Benet 1, 2 , Erik Guillen 1 , Caroline Koch 1 , Saidi M'Homa Soudja 1 , Fabien Delahaye 3, 4 , David Fooksman 1, 2 , Grégoire Lauvau 1
Affiliation  

While cognate antigen drives clonal expansion of memory CD8+ T (CD8+ TM) cells to achieve sterilizing immunity in immunized hosts, not much is known on how cognate antigen contributes to early protection before clonal expansion occurs. Here, using distinct models of immunization, we establish that cognate antigen recognition by CD8+ TM cells on dendritic cells initiates their rapid and coordinated production of a burst of CCL3, CCL4, and XCL1 chemokines under the transcriptional control of interferon (IFN) regulatory factor 4. Using intravital microscopy imaging, we reveal that CD8+ TM cells undergo antigen-dependent arrest in splenic red pulp clusters of CCR2+Ly6C+ monocytes to which they deliver IFNγ and chemokines. IFNγ enables chemokine-induced microbicidal activities in monocytes for protection. Thus, rapid and effective CD8+ TM cell responses require spatially and temporally coordinated events that quickly restrict microbial pathogen growth through the local delivery of activating chemokines to CCR2+Ly6C+ monocytes.

中文翻译:


记忆 CD8+ T 细胞通过向单核细胞簇局部递送趋化因子和 IFNγ 介导早期病原体特异性保护



虽然同源抗原驱动记忆 CD8 + T (CD8 + T M ) 细胞的克隆扩增以在免疫宿主中实现灭菌免疫,但对于同源抗原如何在克隆扩增发生之前促进早期保护知之甚少。在这里,使用不同的免疫模型,我们确定树突状细胞上的 CD8 + T M细胞识别同源抗原,在干扰素 (IFN) 调节的转录控制下启动 CCL3、CCL4 和 XCL1 趋化因子的快速协调产生。因子 4。利用活体显微镜成像,我们揭示了 CD8 + T M细胞在 CCR2 + Ly6C +单核细胞的脾红髓簇中经历抗原依赖性停滞,并向其中传递 IFNγ 和趋化因子。 IFNγ 能够在单核细胞中实现趋化因子诱导的杀菌活性,从而起到保护作用。因此,快速有效的 CD8 + T M细胞反应需要空间和时间上协调的事件,通过向 CCR2 + Ly6C +单核细胞局部递送活化趋化因子来快速限制微生物病原体的生长。
更新日期:2021-09-01
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