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健康状态以及埃博拉和尼帕病毒感染期间人类和灵长类动物组织中的细胞免疫表型分析。

Cellular immunophenotyping in human and primate tissues during healthy conditions and Ebola and Nipah infections.

作者信息

Platt Andrew P, Barr Bobbi, Marketon Anthony, Bernbaum Rebecca, Rivera Deja Fp, Munster Vincent J, Chertow Daniel S, Holbrook Michael R, Anthony Scott M, Pahar Bapi

机构信息

Laboratory of Virology, National Institute of Allergy and Infectious Diseases.

Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, and.

出版信息

JCI Insight. 2025 Apr 17;10(11). doi: 10.1172/jci.insight.185861. eCollection 2025 Jun 9.

DOI:10.1172/jci.insight.185861
PMID:40244690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12220940/
Abstract

We developed a 29-color spectral cytometry panel to enhance nonhuman primate (NHP) models for cross-reactive immunophenotyping. This panel is suitable for biosafety level 4 (BSL-4) viruses and can be used with both human and NHP samples in BSL-2 research settings. Tissues from humans, rhesus monkeys (RhMs), crab-eating macaques (CEMs), and green monkeys (GMs) were stained with a 29-color immunophenotyping panel requiring only 2 clone substitutions. Comparable staining was observed for all samples. Unbiased analysis showed acceptable overlap in T cell phenotypes across samples, with differences in human and NHP B cells and granulocytes. In CEMs, most circulating CD8+ T cells were from effector memory cells, with significantly higher levels than in humans, RhMs, and GMs. Analysis of samples from various anatomical sites revealed distinct location-specific phenotypes. In Nipah virus-exposed animals, splenocytes showed a substantial increase in IgM+ B cells and a reduction in effector memory CD8+ T cells compared with unexposed controls. Lymph nodes from Ebola virus-exposed animals showed a loss of CXCR3+CD8+ T cells versus unexposed controls. This panel may guide the development of additional multicolor panels in preclinical and clinical settings and may increase understanding of the pathogenesis of diseases caused by emerging and reemerging viruses.

摘要

我们开发了一种29色光谱细胞术检测板,以增强非人类灵长类动物(NHP)模型用于交叉反应免疫表型分析。该检测板适用于生物安全4级(BSL-4)病毒,并且可在BSL-2研究环境中用于人类和NHP样本。来自人类、恒河猴(RhM)、食蟹猕猴(CEM)和绿猴(GM)的组织用仅需2个克隆替换的29色免疫表型检测板进行染色。所有样本均观察到可比的染色情况。无偏分析显示不同样本间T细胞表型存在可接受的重叠,而人类和NHP的B细胞及粒细胞存在差异。在食蟹猕猴中,大多数循环CD8+ T细胞来自效应记忆细胞,其水平显著高于人类、恒河猴和绿猴。对来自不同解剖部位的样本分析揭示了不同的部位特异性表型。在感染尼帕病毒的动物中,与未感染对照相比,脾细胞中IgM+ B细胞大幅增加,效应记忆CD8+ T细胞减少。与未感染对照相比,感染埃博拉病毒动物的淋巴结中CXCR3+CD8+ T细胞减少。该检测板可能会指导临床前和临床环境中其他多色检测板的开发,并可能增进对由新出现和重新出现的病毒引起的疾病发病机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/871946c41f16/jciinsight-10-185861-g186.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/81613e234040/jciinsight-10-185861-g183.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/99e63a20b21c/jciinsight-10-185861-g184.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/7c861097336f/jciinsight-10-185861-g185.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/871946c41f16/jciinsight-10-185861-g186.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/81613e234040/jciinsight-10-185861-g183.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/99e63a20b21c/jciinsight-10-185861-g184.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/7c861097336f/jciinsight-10-185861-g185.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07e0/12220940/871946c41f16/jciinsight-10-185861-g186.jpg

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Depletion of Bone Marrow Hematopoietic Cells in Ebolavirus-Infected Rhesus Macaques: A Possible Cause of Hematologic Abnormalities in Ebolavirus Disease.埃博拉病毒感染恒河猴骨髓造血细胞耗竭:埃博拉病毒病血液学异常的可能原因。
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