Cytolytic CD8+ T cell response to SARS-CoV-2 and non-SARS-CoV-2-related viruses is associated with severe manifestation of COVID-19

Kristina Allers; Verena Moos; Jörg Hofmann; Mario Witkowski; Hildrun Haibel; Stefan Angermair; Thomas Schneider

doi:10.1016/j.clim.2023.109712

Cytolytic CD8⁺ T cell response to SARS-CoV-2 and non-SARS-CoV-2-related viruses is associated with severe manifestation of COVID-19

Clin Immunol. 2023 Sep:254:109712. doi: 10.1016/j.clim.2023.109712. Epub 2023 Jul 26.

Authors

Kristina Allers¹, Verena Moos², Jörg Hofmann³, Mario Witkowski⁴, Hildrun Haibel², Stefan Angermair⁵, Thomas Schneider²

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. Electronic address: [email protected].
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Division of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
³ Labor Berlin - Charité Vivantes GmbH, Sylter Straße 2, 13353 Berlin, Germany.
⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Microbiology, Infectious Diseases and Immunology, Laboratory of Innate Immunity, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany.

PMID: 37506745
DOI: 10.1016/j.clim.2023.109712

Abstract

Little is known about the CD8⁺ T cell functionality in the coronavirus disease 2019 (COVID-19). Therefore, we examined twenty-five hospitalized COVID-19 patients with moderate (MD) or severe disease (SD) as well as seventeen SARS-CoV-2-unexposed persons regarding the cytolytic and cytokine-producing reactivity of their CD8⁺ T cells. Reactive CD8⁺ T cells were detectable in 90% of the unexposed persons, confirming high cross-reactive immune memory in the general population. Compared to unexposed persons and MD patients, SD patients had higher numbers of SARS-CoV-2 reactive CD8⁺ T cells with cytolytic function that can simultaneously produce inflammatory cytokines. In addition, SD patients showed higher CD8⁺ T cell reactivity against non-SARS-CoV-2-related viruses, which was mainly mediated by cytolytic response. Sequence alignments showed that cross-reactivities with the Spike protein could contribute to the expansion of such cells. Since insufficiently regulated cytolytic CD8⁺ T cells can damage peripheral and vascular tissue structures, high levels of both SARS-CoV-2-reactive and heterologously activated cytolytic CD8⁺ T cells could favor severe disease progression.

Keywords: Bystander activation; CD8(+) T cell response; COVID-19; Cytolytic CD8(+) T cells; Heterologous T cell activation; SARS-CoV-2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
COVID-19*
Humans
SARS-CoV-2
T-Lymphocytes, Cytotoxic