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SARS-CoV-2 表位特异性 CD4 记忆 T 细胞应答与 COVID-19 疾病严重程度和抗体持久性的关系。

SARS-CoV-2 epitope-specific CD4 memory T cell responses across COVID-19 disease severity and antibody durability.

机构信息

Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Sci Immunol. 2022 Jul 22;7(73):eabl9464. doi: 10.1126/sciimmunol.abl9464.


DOI:10.1126/sciimmunol.abl9464
PMID:35857584
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9097883/
Abstract

CD4 T cells are central to long-term immunity against viruses through the functions of T helper 1 (T1) and T follicular helper (T) cell subsets. To better understand the role of these subsets in coronavirus disease 2019 (COVID-19) immunity, we conducted a longitudinal study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4 T cell and antibody responses in convalescent individuals who seroconverted during the first wave of the pandemic in Boston, MA, USA, across a range of COVID-19 disease severities. Analyses of spike (S) and nucleocapsid (N) epitope-specific CD4 T cells using peptide and major histocompatibility complex class II (pMHCII) tetramers demonstrated expanded populations of T cells recognizing the different SARS-CoV-2 epitopes in most individuals compared with prepandemic controls. Individuals who experienced a milder disease course not requiring hospitalization had a greater percentage of circulating T (cT) and T1 cells among SARS-CoV-2-specific cells. Analysis of SARS-CoV-2-specific CD4 T cells responses in a subset of individuals with sustained anti-S antibody responses after viral clearance also revealed an increased proportion of memory cT cells. Our findings indicate that efficient early disease control also predicts favorable long-term adaptive immunity.

摘要

CD4 T 细胞通过 T 辅助 1(T1)和滤泡辅助 T(Tfh)细胞亚群的功能,对长期抗病毒免疫起着核心作用。为了更好地了解这些亚群在 2019 冠状病毒病(COVID-19)免疫中的作用,我们对美国马萨诸塞州波士顿市大流行第一波期间发生血清转换的康复个体的严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)特异性 CD4 T 细胞和抗体反应进行了纵向研究,涵盖了一系列 COVID-19 疾病严重程度。使用肽和主要组织相容性复合物 II(pMHCII)四聚体分析棘突(S)和核衣壳(N)表位特异性 CD4 T 细胞,与大流行前对照相比,大多数个体中识别不同 SARS-CoV-2 表位的 T 细胞群体有所扩大。与需要住院治疗的轻症患者相比,无住院治疗的轻症患者的循环 T(cT)和 T1 细胞在 SARS-CoV-2 特异性细胞中的比例更高。对病毒清除后持续产生抗-S 抗体反应的个体中的 SARS-CoV-2 特异性 CD4 T 细胞反应进行分析,也揭示了记忆性 cT 细胞的比例增加。我们的研究结果表明,早期有效控制疾病也预示着良好的长期适应性免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/244dafedb4f2/sciimmunol.abl9464-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/fc05fe3a71c5/sciimmunol.abl9464-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/f6d8754e01b2/sciimmunol.abl9464-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/183416043c3f/sciimmunol.abl9464-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/d091b954b4ba/sciimmunol.abl9464-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/fdaaafa34c3b/sciimmunol.abl9464-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/244dafedb4f2/sciimmunol.abl9464-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/fc05fe3a71c5/sciimmunol.abl9464-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/f6d8754e01b2/sciimmunol.abl9464-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/183416043c3f/sciimmunol.abl9464-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/d091b954b4ba/sciimmunol.abl9464-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/fdaaafa34c3b/sciimmunol.abl9464-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc1d/9097883/244dafedb4f2/sciimmunol.abl9464-f6.jpg

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本文引用的文献

[1]
Cross-reactive and mono-reactive SARS-CoV-2 CD4+ T cells in prepandemic and COVID-19 convalescent individuals.

PLoS Pathog. 2021-12

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Sci Immunol. 2021-1-21

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Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection.

Science. 2021-2-5

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Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19.

Cell. 2021-1-7

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