Three phases of CD8 T cell response in the lung following H1N1 influenza infection and sphingosine 1 phosphate agonist therapy.
Three phases of CD8 T cell response in the lung following H1N1 influenza infection and sphingosine 1 phosphate agonist therapy.
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DOI：
10.1371/journal.pone.0058033
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cahalan MD
中科院分区：
文献类型：
--
作者：
Matheu MP;Teijaro JR;Walsh KB;Greenberg ML;Marsolais D;Parker I;Rosen H;Oldstone MB;Cahalan MD
流感诱导的肺水肿和炎症被称为“细胞因子风暴”的细胞因子和趋化因子产生的正反馈回路加剧，这是流感相关发病率和死亡率增加的标志。一旦感染，免疫应答在肺和引流淋巴结中迅速启动，导致病毒特异性效应细胞的扩增。使用双光子显微镜，我们在流感感染后的前两周内对肺部和引流纵隔淋巴结中的树突状细胞（DC）和病毒特异性eGFP+ CD 8 + T细胞的动态进行了成像。揭示了T细胞和CD 11 c + DC行为的三个不同阶段：1）致敏，由肺DC到达淋巴结促进，特征在于抗原特异性CD 8 + T细胞的抗原识别和扩增;经常观察到与DC接触的不对称T细胞分裂。2)清除，在此期间，DC重新填充肺，T细胞离开引流淋巴结并重新进入肺组织，在肺组织中，增大的活动T细胞与DC接触并形成长期相互作用。3)维持，特征在于肺组织的T细胞扫描和从局部抗原呈递细胞解离; T细胞与DC结合的时间更短，并在胶原上快速迁移。单剂量的鞘氨醇-1-磷酸受体激动剂AAL-R足以抑制流感诱导的病毒风暴，改变流感清除期间的T细胞和DC行为，延迟T细胞分裂，肺中的细胞浸润，并抑制肺中的T-DC相互作用。我们的研究结果提供了流感感染期间淋巴结和肺中T细胞和DC编排和动力学的详细描述。此外，我们认为，在T细胞和DC动力学的相位滞后，在体内靶向S1 P受体诱导的免疫反应的强度可能会减弱，并可以操纵治疗的好处。
Influenza-induced lung edema and inflammation are exacerbated by a positive feedback loop of cytokine and chemokine production termed a ‘cytokine storm’, a hallmark of increased influenza-related morbidity and mortality. Upon infection, an immune response is rapidly initiated in the lungs and draining lymph node, leading to expansion of virus-specific effector cells. Using two-photon microscopy, we imaged the dynamics of dendritic cells (DC) and virus-specific eGFP+CD8+ T cells in the lungs and draining mediastinal lymph nodes during the first two weeks following influenza infection. Three distinct phases of T cell and CD11c+ DC behavior were revealed: 1) Priming, facilitated by the arrival of lung DCs in the lymph node and characterized by antigen recognition and expansion of antigen-specific CD8+ T cells; asymmetric T cell division in contact with DCs was frequently observed. 2) Clearance, during which DCs re-populate the lung and T cells leave the draining lymph node and re-enter the lung tissue where enlarged, motile T cells come into contact with DCs and form long-lived interactions. 3) Maintenance, characterized by T-cell scanning of the lung tissue and dissociation from local antigen presenting cells; the T cells spend less time in association with DCs and migrate rapidly on collagen. A single dose of a sphingosine-1-phosphate receptor agonist, AAL-R, sufficient to suppress influenza-induced cytokine-storm, altered T cell and DC behavior during influenza clearance, delaying T cell division, cellular infiltration in the lung, and suppressing T-DC interactions in the lung. Our results provide a detailed description of T cell and DC choreography and dynamics in the lymph node and the lung during influenza infection. In addition, we suggest that phase lags in T cell and DC dynamics induced by targeting S1P receptors in vivo may attenuate the intensity of the immune response and can be manipulated for therapeutic benefit.
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影响因子：
32.4
作者：
Beuneu, Helene;Lemaitre, Fabrice;Bousso, Philippe
通讯作者：
Bousso, Philippe
影响因子：
8.8
作者：
Heyland, DK;Groll, D;Caeser, M
通讯作者：
Caeser, M
DOI：
10.1038/nri3166
发表时间：
2012-03-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.3
作者：
Kim, Taeg S.;Hufford, Matthew M.;Braciale, Thomas J.
通讯作者：
Braciale, Thomas J.
DOI：
10.1084/jem.20091472
发表时间：
2009-11-23
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Halle S;Dujardin HC;Bakocevic N;Fleige H;Danzer H;Willenzon S;Suezer Y;Hämmerling G;Garbi N;Sutter G;Worbs T;Förster R
通讯作者：
Förster R