Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells
Copyright © 2021, American Association for the Advancement of Science..
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.
| Errataetall: | |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
|---|---|
| Enthalten in: |
Science immunology - 6(2021), 55 vom: 21. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Kusnadi, Anthony [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Journal Article |
|---|
| Anmerkungen: |
Date Completed 02.02.2021 Date Revised 11.11.2023 published: Print UpdateOf: bioRxiv. 2020 Jul 10;:. - PMID 32676602 Citation Status MEDLINE |
|---|
| doi: |
10.1126/sciimmunol.abe4782 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM320412245 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM320412245 | ||
| 003 | DE-627 | ||
| 005 | 20231225173527.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1126/sciimmunol.abe4782 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1068.xml |
| 035 | |a (DE-627)NLM320412245 | ||
| 035 | |a (NLM)33478949 | ||
| 035 | |a (PII)eabe4782 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Kusnadi, Anthony |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.02.2021 | ||
| 500 | |a Date Revised 11.11.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a UpdateOf: bioRxiv. 2020 Jul 10;:. - PMID 32676602 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021, American Association for the Advancement of Science. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 700 | 1 | |a Ramírez-Suástegui, Ciro |e verfasserin |4 aut | |
| 700 | 1 | |a Fajardo, Vicente |e verfasserin |4 aut | |
| 700 | 1 | |a Chee, Serena J |e verfasserin |4 aut | |
| 700 | 1 | |a Meckiff, Benjamin J |e verfasserin |4 aut | |
| 700 | 1 | |a Simon, Hayley |e verfasserin |4 aut | |
| 700 | 1 | |a Pelosi, Emanuela |e verfasserin |4 aut | |
| 700 | 1 | |a Seumois, Grégory |e verfasserin |4 aut | |
| 700 | 1 | |a Ay, Ferhat |e verfasserin |4 aut | |
| 700 | 1 | |a Vijayanand, Pandurangan |e verfasserin |4 aut | |
| 700 | 1 | |a Ottensmeier, Christian H |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Science immunology |d 2016 |g 6(2021), 55 vom: 21. Jan. |w (DE-627)NLM263875547 |x 2470-9468 |7 nnns |
| 773 | 1 | 8 | |g volume:6 |g year:2021 |g number:55 |g day:21 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1126/sciimmunol.abe4782 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 6 |j 2021 |e 55 |b 21 |c 01 | ||