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队列研究中 CD4 和 CD8 T 细胞介导的抗甲型流感病毒保护作用的研究。

Investigation of CD4 and CD8 T cell-mediated protection against influenza A virus in a cohort study.

机构信息

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, Special Administrative Region, China.

Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, New Territories, Hong Kong, Special Administrative Region, China.

出版信息

BMC Med. 2022 Jul 21;20(1):230. doi: 10.1186/s12916-022-02429-7.

DOI:10.1186/s12916-022-02429-7
PMID:35858844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9301821/
Abstract

BACKGROUND

The protective effect of T cell-mediated immunity against influenza virus infections in natural settings remains unclear, especially in seasonal epidemics.

METHODS

To explore the potential of such protection, we analyzed the blood samples collected longitudinally in a community-based study and covered the first wave of pandemic H1N1 (pH1N1), two subsequent pH1N1 epidemics, and three seasonal H3N2 influenza A epidemics (H3N2) for which we measured pre-existing influenza virus-specific CD4 and CD8 T cell responses by intracellular IFN-γ staining assay for 965 whole blood samples.

RESULTS

Based on logistic regression, we found that higher pre-existing influenza virus-specific CD4 and CD8 T cell responses were associated with lower infection odds for corresponding subtypes. Every fold increase in H3N2-specific CD4 and CD8 T cells was associated with 28% (95% CI 8%, 44%) and 26% (95% CI 8%, 41%) lower H3N2 infection odds, respectively. Every fold increase in pre-existing seasonal H1N1 influenza A virus (sH1N1)-specific CD4 and CD8 T cells was associated with 28% (95% CI 11%, 41%) and 22% (95% CI 8%, 33%) lower pH1N1 infection odds, respectively. We observed the same associations for individuals with pre-epidemic hemagglutination inhibition (HAI) titers < 40. There was no correlation between pre-existing influenza virus-specific CD4 and CD8 T cell response and HAI titer.

CONCLUSIONS

We demonstrated homosubtypic and cross-strain protection against influenza infections was associated with T cell response, especially CD4 T cell response. These protections were independent of the protection associated with HAI titer. Therefore, T cell response could be an assessment of individual and population immunity for future epidemics and pandemics, in addition to using HAI titer.

摘要

背景

T 细胞介导的免疫对流感病毒感染的保护作用在自然环境中仍不清楚,特别是在季节性流行中。

方法

为了探索这种保护的潜力,我们分析了在基于社区的研究中纵向采集的血液样本,该研究涵盖了大流行 H1N1(pH1N1)的第一波、随后的两波 pH1N1 流行以及三波季节性 H3N2 甲型流感(H3N2)流行。我们通过细胞内 IFN-γ染色测定法测量了 965 份全血样本中预先存在的流感病毒特异性 CD4 和 CD8 T 细胞反应。

结果

基于逻辑回归,我们发现较高的预先存在的流感病毒特异性 CD4 和 CD8 T 细胞反应与相应亚型的感染几率降低有关。H3N2 特异性 CD4 和 CD8 T 细胞每增加一倍,H3N2 感染的几率分别降低 28%(95%CI 8%,44%)和 26%(95%CI 8%,41%)。预先存在的季节性甲型流感病毒(sH1N1)特异性 CD4 和 CD8 T 细胞每增加一倍,pH1N1 感染的几率分别降低 28%(95%CI 11%,41%)和 22%(95%CI 8%,33%)。对于血凝抑制(HAI)滴度<40 的个体,我们观察到了相同的关联。预先存在的流感病毒特异性 CD4 和 CD8 T 细胞反应与 HAI 滴度之间没有相关性。

结论

我们证明了同种亚型和交叉株对流感感染的保护作用与 T 细胞反应有关,特别是 CD4 T 细胞反应。这些保护作用独立于与 HAI 滴度相关的保护作用。因此,T 细胞反应可以作为评估个体和人群对未来流行和大流行的免疫能力的指标,除了使用 HAI 滴度之外。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/2b4d7a36d41b/12916_2022_2429_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/0685b267e254/12916_2022_2429_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/6f277c7c9384/12916_2022_2429_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/3fd2c59ced32/12916_2022_2429_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/297f7ee93fa2/12916_2022_2429_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/2b4d7a36d41b/12916_2022_2429_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/0685b267e254/12916_2022_2429_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/bd4f9d44c934/12916_2022_2429_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/6f277c7c9384/12916_2022_2429_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/3fd2c59ced32/12916_2022_2429_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/297f7ee93fa2/12916_2022_2429_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/045c/9301821/2b4d7a36d41b/12916_2022_2429_Fig6_HTML.jpg

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