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

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 BalfanzChristian Kurts, Gernot Marx, Nikolaus Marx, Michael Dreher, Rebekka K. Schneider, Julio Saez-Rodriguez, Ivan Costa, Sikander Hayat, Rafael Kramann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)
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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 NK-like CD8+ T cells in COVID-19 severity.

Original languageEnglish
Article number1066176
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 16 Dec 2022

Bibliographical note

Funding:
German Research Foundation grant DFG: KR 4073/11-1
(RK). German Research Foundation grant SFBTRR219, Project
ID 322900939 (RK). German Research Foundation grant
CRU344, P1 (RK). European Research Council grant ERC-StG
677448 (RK). State of North Rhine-Westphalia grant Return to
NRW (RK). BMBF grant NUM-COVID19, Organo-Strat
01KX2021 (RK). CRU5011 (RK). ERC-CoG 101043403 (RK).
German Research Foundation grant CRU 344, Z (IC). BMBF
grant eMed Consortia Fibromap (RK, RS, IC). Bioinformatics
DATa ENvironment (BioDATEN) project (EF).

Publisher Copyright:
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.

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