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免疫功能低下的肾移植受者中激活的滤泡辅助 T 细胞导致 SARS-CoV-2 特异性反应受损。

Impaired SARS-CoV-2-specific responses via activated T follicular helper cells in immunocompromised kidney transplant recipients.

机构信息

Department of Transplant Surgery, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

Department of Virology, Division of Host Defense Mechanism, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

出版信息

Sci Rep. 2024 Oct 19;14(1):24571. doi: 10.1038/s41598-024-76251-x.

DOI:10.1038/s41598-024-76251-x
PMID:39427014
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11490627/
Abstract

Activated T follicular helper (aTfh) cells are likely important in host immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. We characterized the immune responses of aTfh cells to the second (D2) and third (booster; D3) doses of an mRNA vaccine in the peripheral blood of 40 kidney transplant recipients (KTRs) and 17 healthy control volunteers (HCs). A significant increase in SARS-CoV-2-specific IgG antibody was seen after D3 in the KTRs; nonetheless, the levels after D2 and D3 were significantly lower than in the HCs. After D2, dramatic increases in activated CD45RACXCR5ICOSPD1 circulating Tfh (acTfh) cells were observed in the HCs, as well as the seropositive patients among the KTRs, when compared with the seronegative patients among the KTRs. Unlike the HCs, KTRs had less prominent immune responses, including the acTfh and T cells that produce interferon gamma, tumor necrosis factor alpha, and interleukin 21. In addition, the increase in acTfh cells was significantly associated with anti-IgG antibody levels after D3. These results indicate impaired SARS-CoV-2-specific responses via acTfh cells in KTRs, and they suggest that acTfh cells in peripheral blood may play an important role in antibody maintenance following SARS-CoV-2 mRNA vaccination.

摘要

活化的滤泡辅助性 T 细胞(aTfh)可能在宿主对严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)mRNA 疫苗的免疫反应中起重要作用。我们描述了 aTfh 细胞对 40 名肾移植受者(KTR)和 17 名健康对照志愿者(HC)外周血中 mRNA 疫苗第二(D2)和第三(加强针;D3)剂的免疫反应。KTR 中在 D3 后观察到 SARS-CoV-2 特异性 IgG 抗体显著增加;然而,D2 和 D3 后的水平明显低于 HCs。在 D2 后,HCs 以及 KTR 中的血清阳性患者中观察到循环 Tfh(acTfh)细胞的活化 CD45RACXCR5ICOSPD1 显著增加,而 KTR 中的血清阴性患者则没有。与 HCs 不同,KTR 的免疫反应不那么明显,包括产生干扰素 γ、肿瘤坏死因子 α 和白细胞介素 21 的 acTfh 和 T 细胞。此外,acTfh 细胞的增加与 D3 后抗 IgG 抗体水平显著相关。这些结果表明,KTR 中通过 acTfh 细胞的 SARS-CoV-2 特异性反应受损,并且它们表明外周血中的 acTfh 细胞可能在 SARS-CoV-2 mRNA 疫苗接种后抗体维持中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/4bd6b805f412/41598_2024_76251_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/9a54864c10fa/41598_2024_76251_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/dea87af0c229/41598_2024_76251_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/99c68986b10d/41598_2024_76251_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/34f70172ec16/41598_2024_76251_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/4bd6b805f412/41598_2024_76251_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/9a54864c10fa/41598_2024_76251_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/dea87af0c229/41598_2024_76251_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/99c68986b10d/41598_2024_76251_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/34f70172ec16/41598_2024_76251_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1d1/11490627/4bd6b805f412/41598_2024_76251_Fig5_HTML.jpg

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本文引用的文献

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The role of interleukin-21 in COVID-19 vaccine-induced B cell-mediated immune responses in patients with kidney disease and kidney transplant recipients.白细胞介素-21 在 COVID-19 疫苗诱导的肾病患者和肾移植受者 B 细胞介导的免疫应答中的作用。
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