体液免疫缺陷患者体内 SARS-CoV-2 相关 T 细胞应答。

SARS-CoV-2-Associated T-Cell Responses in the Presence of Humoral Immunodeficiency.

机构信息

Division of Basic and Clinical Immunology, University of California, Irvine, California, USA,

Division of Basic and Clinical Immunology, University of California, Irvine, California, USA.

出版信息

Int Arch Allergy Immunol. 2021;182(3):195-209. doi: 10.1159/000514193. Epub 2021 Jan 22.

Abstract

We report perhaps the most comprehensive study of subsets of CD4+ and CD8+ and subsets of B cells in a mild symptomatic SARS-CoV-2+ immunocompetent patient and a common variable immunodeficiency disease (CVID) patient who had normal absolute lymphocyte counts and remained negative for SARS-CoV-2 IgG antibodies. Naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated effector memory (TEMRA) subsets of CD4+ and CD8+ T cells, subsets of T follicular helper cells (cTFH, TFH1, TFH2, TFH17, TFH1/TFH17, and TFR), CD4 Treg, CD8 Treg, mature B cells, transitional B cells, marginal zone B cells, germinal center (GC) B cells, CD21low B cells, antibody-secreting cells (plasmablasts), and Breg cells were examined in patients and age-matched controls with appropriate monoclonal antibodies and isotype controls using multicolor flow cytometry. Different patterns of abnormalities (often contrasting) were observed in the subsets of CD4+ T, CD8+ T, B-cell subsets, and regulatory lymphocytes among the immunocompetent patient and CVID patient as compared to corresponding healthy controls. Furthermore, when data were analyzed between the 2 patients, the immunocompetent patient demonstrated greater changes in various subsets as compared to the CVID patient. These data demonstrate different immunological responses to SARS-CoV-2 infection in an immunocompetent patient and the CVID patient. A marked decrease in GC B cells and plasmablasts may be responsible for failure to make SARS-CoV-2 antibodies. The lack of SARS-CoV-2 antibodies with mild clinical disease suggests an important role of T-cell response in defense against SARS-CoV-2 infection.

摘要

我们报告了一项或许是最全面的研究,研究对象是一名轻症有症状的 SARS-CoV-2 感染免疫功能正常患者和一名普通变异型免疫缺陷病(CVID)患者,这两名患者的绝对淋巴细胞计数正常,且 SARS-CoV-2 IgG 抗体检测结果均为阴性。我们检测了 CD4+ 和 CD8+ T 细胞的初始(TN)、中央记忆(TCM)、效应记忆(TEM)和终末分化效应记忆(TEMRA)亚群、滤泡辅助 T 细胞(cTFH、TFH1、TFH2、TFH17、TFH1/TFH17 和 TFR)亚群、CD4 Treg、CD8 Treg、成熟 B 细胞、过渡 B 细胞、边缘区 B 细胞、生发中心(GC)B 细胞、CD21low B 细胞、抗体分泌细胞(浆母细胞)和 Breg 细胞,采用多色流式细胞术,使用适当的单克隆抗体和同型对照,对患者和年龄匹配的对照进行了检测。与相应的健康对照相比,免疫功能正常患者和 CVID 患者的 CD4+ T、CD8+ T、B 细胞亚群和调节性淋巴细胞亚群中观察到不同模式的异常(通常相反)。此外,当对这两名患者的数据进行分析时,与 CVID 患者相比,免疫功能正常患者的各种亚群变化更大。这些数据表明,免疫功能正常患者和 CVID 患者对 SARS-CoV-2 感染的免疫反应不同。GC B 细胞和浆母细胞的显著减少可能是未能产生 SARS-CoV-2 抗体的原因。轻度临床疾病但缺乏 SARS-CoV-2 抗体提示 T 细胞反应在防御 SARS-CoV-2 感染方面发挥着重要作用。

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