Division of Basic and Clinical Immunology, University of California, Irvine, California, USA,
Division of Basic and Clinical Immunology, University of California, Irvine, California, USA.
Int Arch Allergy Immunol. 2021;182(3):195-209. doi: 10.1159/000514193. Epub 2021 Jan 22.
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.
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。
