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STTT：新冠肺炎重症和轻症患者对新冠病毒感染的适应性免疫反应差异较大

2020-08-20 哈尔滨工业大学 哈尔滨工业大学

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近日，哈尔滨工业大学黄志伟教授课题组在国际知名期刊Nature子刊Signal Transduction and Targeted Therapy杂志发表关于新冠肺炎的最新研究成果，题目为&ldquo

近日，哈尔滨工业大学黄志伟教授课题组在国际知名期刊Nature子刊Signal Transduction and Targeted Therapy杂志发表关于新冠肺炎的最新研究成果，题目为“新冠肺炎重症和轻症患者对新冠病毒感染的适应性免疫反应"。本研究对于理解重症和轻症患者的发病和康复机制，以及设计防治SARS-CoV-2感染的疫苗和治疗药物具有重要意义。

截至2020年6月，SARS-CoV-2引起的全球范围的新冠肺炎疫情已经影响到800多万人，为了研究COVID-19患者针对SARS-CoV-2感染的适应性免疫反应机制及康复患者的免疫记忆建立情况，该团队首先应用单细胞转录组和免疫组（TCR/BCR）高通量测序数据，并结合功能实验对疾病严重程度不同的COVID-19患者（重症和轻症）外周血中适应性免疫细胞的响应机制进行了研究，揭示了T/B细胞针对SARS-CoV-2感染而进行的免疫组库重建特征，以及COVID-19诱导的外周血淋巴细胞亚群组成变化特征，发现了T细胞免疫记忆和B细胞体液免疫反应程度与疾病严重程度存在一定的正相关性，以及重症和轻症患者不同的免疫学变化特征（见下图）。

 

图一 COVID-19患者针对SARS-CoV-2感染的适应性免疫反应及免疫记忆建立情况

该研究首先发现，相比于健康人，COVID-19患者表达细胞毒性分子（如GZMA、GZMB、PRF1、NKG7）的杀伤性T细胞亚群（CD8+效应记忆细胞（CD8+ TEM）、表达CD45RA的CD8+ TEM细胞亚群（CD8+ TTE）和CD4+TTE）的占比提高，表明这些杀伤性T细胞的增殖与COVID-19有关；同时发现COVID-19患者中的黏膜相关恒定T淋巴细胞（MAIT）显著减少；而SARS-CoV-2诱导的Gamma/delta T细胞消耗在恢复期患者中得到一定程度的恢复，但仍未完全恢复到正常水平，这些结果表明COVID-19患者的适应性免疫系统在康复早期并未得到完全恢复。为了识别恢复期COVID-19患者中SARS-CoV-2特异性T细胞亚群，团队首先通过scRNA-seq和scTCR-seq研究不同T细胞亚群的克隆扩增情况，发现对SARS-CoV-2响应的主要T细胞亚群包括CD8+ TEM、CD8+ TTE和CD4+TTE，相较于轻症患者，重症患者对于SARS-CoV-2具有更强的记忆T细胞反应性。在B细胞免疫反应方面，发现更强烈的体液免疫反应是重症患者的典型特点。进一步评估早期康复患者适应性免疫系统的恢复情况，发现在COVID-19患者的康复早期促炎细胞因子可能已经恢复到正常水平。

此外，本研究还发现了不同COVID-19患者的抗病毒反应存在很大的异质性，同时也提示了不同个体存在不同的抗病毒反应机制的可能性，给后续更大规模的队列研究提出了更多的可能性。这项研究对于理解重症和轻症患者的发病和康复机制，以及设计防治SARS-CoV-2感染的疫苗和治疗药物具有重要意义。

哈尔滨工业大学生命学院副教授张帆、硕士研究生甘锐、博士研究生甄梓期、黑龙江省医院感染科主任胡晓丽为该研究论文的并列第一作者，博士研究生李想和周凤侠对本研究做出了重要贡献。本研究受到国家自然科学基金委、哈工大青年科学家工作室、哈工大新冠疫情应急科研攻关项目等基金的资助。

原始出处：Fan Zhang,  Rui Gan,  Ziqi Zhen, et al. adaptive immune responses to SARS-CoV-2 infection in severe versus mild individuals. Singal Transduct Tar.

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    2020-08-21 linagood

    #适应性免疫#

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    2020-08-22 cnxcy

    #免疫反应#

    0

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    2020-08-22 智慧医人

    #适应性#

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    2020-08-20 公卫新人

    新冠肺炎，疫情何时才能消失

    0