Turner D L, Bickham K L, Thome J J, Kim C Y, D'Ovidio F, Wherry E J, Farber D L
1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA [2] Department of Medicine, Columbia University Medical Center, New York, New York, USA.
1] Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA [2] Department of Microbiology and Immunology, Columbia University Medical Center, New York, New York, USA.
Mucosal Immunol. 2014 May;7(3):501-10. doi: 10.1038/mi.2013.67. Epub 2013 Sep 25.
The extent to which tissue-specific viral infections generate memory T cells specifically adapted to and maintained within the target infection site is unknown. Here, we show that respiratory virus-specific memory T cells in mice and humans are generated and maintained in compartmentalized niches in lungs, distinct from populations in lymphoid tissue or circulation. Using a polyclonal mouse model of influenza infection combined with an in vivo antibody labeling approach and confocal imaging, we identify a spatially distinct niche in the lung where influenza-specific T-cell responses are expanded and maintained long term as tissue-resident memory (T(RM)) CD4 and CD8 T cells. Lung T(RM) are further distinguished from circulating memory subsets in lung and spleen based on CD69 expression and persistence independent of lymphoid stores. In humans, influenza-specific T cells are enriched within the lung T(RM) subset, whereas memory CD8 T cells specific for the systemic virus cytomegalovirus are distributed in both lung and spleen, suggesting that the site of infection affects T(RM) generation. Our findings reveal a precise spatial organization to virus-specific T-cell memory, determined by the site of the initial infection, with important implications for the development of targeted strategies to boost immunity at appropriate tissue sites.
组织特异性病毒感染在何种程度上会产生专门适应并维持在靶感染部位的记忆T细胞尚不清楚。在此，我们表明，小鼠和人类中呼吸道病毒特异性记忆T细胞是在肺内分隔的小生境中产生和维持的，这与淋巴组织或循环中的细胞群体不同。利用流感感染的多克隆小鼠模型，结合体内抗体标记方法和共聚焦成像，我们在肺中确定了一个空间上独特的小生境，在那里流感特异性T细胞反应作为组织驻留记忆（T(RM)）CD4和CD8 T细胞长期扩展和维持。基于CD69表达和不依赖于淋巴储备的持久性，肺T(RM)进一步与肺和脾中的循环记忆亚群区分开来。在人类中，流感特异性T细胞在肺T(RM)亚群中富集，而针对全身性病毒巨细胞病毒的记忆CD8 T细胞则分布在肺和脾中，这表明感染部位会影响T(RM)的产生。我们的研究结果揭示了病毒特异性T细胞记忆的精确空间组织，由初始感染部位决定，这对制定在适当组织部位增强免疫力的靶向策略具有重要意义。
