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- Title
Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling.
- Authors
Schreibing, Felix; Hannani, Monica T.; Hyojin Kim; Nagai, James S.; Ticconi, Fabio; Fewings, Eleanor; Bleckwehl, Tore; Begemann, Matthias; Torow, Natalia; Kuppe, Christoph; Kurth, Ingo; Kranz, Jennifer; Frank, Dario; Anslinger, Teresa M.; Ziegler, Patrick; Kraus, Thomas; Enczmann, Jürgen; Balz, Vera; Windhofer, Frank; Balfanz, Paul
- Abstract
Introduction: SARS-CoV-2 infection results in varying disease severity, ranging from asymptomatic infection to severe illness. A detailed understanding of the immune response to SARS-CoV-2 is critical to unravel the causative factors underlying differences in disease severity and to develop optimal vaccines against new SARS-CoV-2 variants. Methods: We combined single-cell RNA and T cell receptor sequencing with CITE-seq antibodies to characterize the CD8+ T cell response to SARS-CoV-2 infection at high resolution and compared responses between mild and severe COVID-19. Results: We observed increased CD8+ T cell exhaustion in severe SARS-CoV-2 infection and identified a population of NK-like, terminally differentiated CD8+ effector T cells characterized by expression of FCGR3A (encoding CD16). Further characterization of NK-like CD8+ T cells revealed heterogeneity among CD16+ NK-like CD8+ T cells and profound differences in cytotoxicity, exhaustion, and NK-like differentiation between mild and severe disease conditions. Discussion: We propose a model in which differences in the surrounding inflammatory milieu lead to crucial differences in NK-like differentiation of CD8+ effector T cells, ultimately resulting in the appearance of NK-like CD8+ T cell populations of different functionality and pathogenicity. Our in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection provides a basis for further investigation of the importance of NKlike CD8+ T cells in COVID-19 severity.
- Subjects
T cells; CD8 antigen; T cell receptors; SARS-CoV-2; CELL populations
- Publication
Frontiers in Immunology, 2022, Vol 13, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2022.1066176