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. 2021 Dec 28;185(3):493–512.e25. doi: 10.1016/j.cell.2021.12.040

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© 2022 The Authors

Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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Accumulation of HLA-DR^hiCD38^hi highly activated but also CD16 expressing CD4⁺ and CD8⁺ T cells in severe COVID-19

(A) Overview of the study cohort and methodological pipeline. Samples were collected from mild and severe COVID-19 patients during the acute and convalescent phase enrolled in Berlin (cohort 1), Bonn (cohort 2), or Aachen (cohort 3), patients suffering from other acute respiratory infections (FLI, being chronically infected HIV, or HBV, patients with non-infectious ARDS as well as controls. CyTOF and scRNA-seq combined with VDJ-seq-based T cell clonotype identification were used to determine COVID-19 as well as severity-specific alterations in the T cell compartment. The obtained results together with serum proteomics and in situ immunofluorescence data were used to develop hypotheses on their functional properties and inducing mechanisms, which were tested in ex vivo cultures. Detailed sample information included in all reported assays can be found in Table S1.

(B and C) UMAPs generated of CD4⁺ (left), CD8⁺ (middle), and TCRgd⁺ (right) T cells from CyTOF. Cells are colored according to donor (B) or cluster (C) origin. For visualization purposes, each UMAP shows 30,000 cells.

(D) Heatmap of CyTOF data (covering CD4⁺ (left panel), CD8⁺ (middle panel), and TCRgd⁺ (right panel) T cells. Z score standardized staining intensity of each marker (rows) per cluster (1–48, in columns, lower part). Clusters were grouped into metaclusters, as defined by the numbers 1–13 (in columns, upper part). Significance levels of differential cluster frequency for the following groups: controls (n = 9), FLI (n = 8), HIV (n = 6), HBV (n = 5), mild acute COVID-19 (n = 28), and severe acute COVID-19 (n = 35). Kruskall-Wallis test and post hoc Dunn’s multiple comparison test. All combinations where tested, only comparisons with healthy controls are shown.

(E) Box plots of CD4⁺ (7, 8, 18) and CD8⁺ (25, 26) T cell clusters determined by CyTOF generated from controls (n = 9), FLI (n = 8), HIV (n = 6), HBV (n = 5), mild acute COVID-19 (n = 20), and severe acute COVID-19 (n = 23) patient samples. Kruskall-Wallis test and post hoc Dunn’s multiple comparison test. KW^∗: adjusted p value (Benjamini-Hochberg) of a Kruskal-Wallis test. All combinations where tested, only comparisons with healthy controls are shown (^∗p < 0.1, ^∗∗p < 0.01,^∗∗∗p < 0.001,^∗∗∗∗p < 0.0001).