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Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell immunoprofiling.

Frontiers in immunology

Authors: Felix Schreibing, Monica T Hannani, Hyojin Kim, James S Nagai, Fabio Ticconi, Eleanor Fewings, Tore Bleckwehl, Matthias Begemann, Natalia Torow, Christoph Kuppe, Ingo Kurth, Jennifer Kranz, Dario Frank, Teresa M Anslinger, Patrick Ziegler, Thomas Kraus, Jürgen Enczmann, Vera Balz, Frank Windhofer, Paul Balfanz, Christian Kurts, Gernot Marx, Nikolaus Marx, Michael Dreher, Rebekka K Schneider, Julio Saez-Rodriguez, Ivan Costa, Sikander Hayat, Rafael Kramann

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 (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 NK-like CD8 T cells in COVID-19 severity.

Copyright © 2022 Schreibing, Hannani, Kim, Nagai, Ticconi, Fewings, Bleckwehl, Begemann, Torow, Kuppe, Kurth, Kranz, Frank, Anslinger, Ziegler, Kraus, Enczmann, Balz, Windhofer, Balfanz, Kurts, Marx, Marx, Dreher, Schneider, Saez-Rodriguez, Costa, Hayat and Kramann.

PMID: 36591270

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