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Science immunology
01 21, 2021;6 (55):

Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8 T cells.

Anthony Kusnadi, Ciro Ramírez-Suástegui, Vicente Fajardo, Serena J Chee, Benjamin J Meckiff, Hayley Simon, Emanuela Pelosi, Grégory Seumois, Ferhat Ay, Pandurangan Vijayanand, Christian H Ottensmeier
Author Information
  1. Anthony Kusnadi: La Jolla Institute for Immunology, La Jolla, CA 92037. ORCID
  2. Ciro Ramírez-Suástegui: La Jolla Institute for Immunology, La Jolla, CA 92037. ORCID
  3. Vicente Fajardo: La Jolla Institute for Immunology, La Jolla, CA 92037. ORCID
  4. Serena J Chee: NIHR and CRUK Southampton Experimental Cancer Medicine Center, Faculty of Medicine, University of Southampton, Southampton, UK. ORCID
  5. Benjamin J Meckiff: La Jolla Institute for Immunology, La Jolla, CA 92037. ORCID
  6. Hayley Simon: La Jolla Institute for Immunology, La Jolla, CA 92037.
  7. Emanuela Pelosi: Southampton Specialist Virology Centre, Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
  8. Grégory Seumois: La Jolla Institute for Immunology, La Jolla, CA 92037. ORCID
  9. Ferhat Ay: La Jolla Institute for Immunology, La Jolla, CA 92037. ORCID
  10. Pandurangan Vijayanand: La Jolla Institute for Immunology, La Jolla, CA 92037. vijay@lji.org cottensmeier@lji.org. ORCID
  11. Christian H Ottensmeier: La Jolla Institute for Immunology, La Jolla, CA 92037. vijay@lji.org cottensmeier@lji.org. ORCID
PMID: 33478949 DOI: 10.1126/sciimmunol.abe4782

Abstract

The molecular properties of CD8 T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8 T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8 T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8 T cell memory responses in patients with severe COVID-19 illness. CD8 T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8 T cells responding to SARS-CoV-2.

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Grants

  1. S10 OD025052/NIH HHS
  2. S10 RR027366/NCRR NIH HHS
  3. R01 HL114093/NHLBI NIH HHS
  4. U19 AI118626/NIAID NIH HHS
  5. U19 AI142742/NIAID NIH HHS
  6. U01 CA260588/NCI NIH HHS
  7. R35 GM128938/NIGMS NIH HHS

MeSH Term

Adult
Aged
Aged, 80 and over
CD8-Positive T-Lymphocytes
COVID-19
Female
Glycolysis
Humans
Immunologic Memory
Male
Middle Aged
NF-kappa B
SARS-CoV-2
Signal Transduction
Single-Cell Analysis
Young Adult

Chemicals

NF-kappa B
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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