Meckiff, Benjamin J, Ramírez-Suástegui, Ciro, Fajardo, Vicente, Chee, Serena J, Kusnadi, Anthony, Simon, Hayley, Grifoni, Alba, Pelosi, Emanuela, Weiskopf, Daniela, Sette, Alessandro et al (show 4 more authors)
(2020)
Single-Cell Transcriptomic Analysis of SARS-CoV-2 Reactive CD4 + T Cells.
SSRN, 1 (07-28).
3641939-.
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2020_Meckff_bioRxiv_Single-cell transcriptomic analysis of SARS-CoV-2 reactive CD4+ T cells.pdf - Submitted version Download (9MB) | Preview |
Abstract
The contribution of CD4+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 32 COVID-19 patients. In patients with severe disease compared to mild disease, we found increased proportions of cytotoxic follicular helper (TFH) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2 reactive regulatory T cells. Importantly, the CD4-CTLs were highly enriched for the expression of transcripts encoding chemokines that are involved in the recruitment of myeloid cells and dendritic cells to the sites of viral infection. Polyfunctional T helper (TH)1 cells and TH17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2 reactive CD4+ T cells in distinct disease severities. Funding: This work was funded by NIH grants U19AI142742 (P.V., A.S., C.H.O), U19AI118626 (P.V., A.S., G.S.), R01HL114093 (P.V., F.A., G.S.,), R35-GM128938 (F.A), S10RR027366 (BD FACSAria-II), S10OD025052 (Illumina Novaseq6000), the William K. Bowes Jr Foundation (P.V.), and Whittaker foundation (P.V., C.H.O.). Supported by the Wessex Clinical Research Network and National Institute of Health Research UK. Conflict of Interest: The authors declare no competing financial interests. Ethical Approval: Ethical approval for this study from the Berkshire Research Ethics Committee 20/SC/0155 and the Ethics Committee of La Jolla Institute for Immunology (LJI) was in place. Written consent was obtained from all subjects.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Prevention, Emerging Infectious Diseases, Vaccine Related, Infectious Diseases, Biodefense, Clinical Research, Pneumonia & Influenza, 2 Aetiology, 2.1 Biological and endogenous factors, Infection, Inflammatory and immune system, 3 Good Health and Well Being |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 10 Nov 2020 10:51 |
| Last Modified: | 12 Apr 2024 14:08 |
| DOI: | 10.2139/ssrn.3641939 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3106351 |
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