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Single-Cell Transcriptomic Analysis of SARS-CoV-2 Reactive CD4 + T Cells

39 Pages Posted: 7 Jul 2020 Publication Status: Review Complete

See all articles by Benjamin J. Meckiff

Benjamin J. Meckiff

La Jolla Institute for Immunology

Ciro Ramírez-Suástegui

La Jolla Institute for Immunology

Vicente Fajardo

La Jolla Institute for Immunology

Serena J. Chee

University of Southampton - Faculty of Medicine

Anthony Kusnadi

La Jolla Institute for Immunology

Hayley Simon

La Jolla Institute for Immunology

Alba Grifoni

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Emanuela Pelosi

University Hospitals NHS Foundation Trust - Southampton Specialist Virology Center

Daniela Weiskopf

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Alessandro Sette

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Ferhat Ay

La Jolla Institute for Allergy and Immunology (LIAI); University of California, San Diego (UCSD) - School of Medicine

Grégory Seumois

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery

Christian Ottensmeier

La Jolla Institute for Immunology

Pandurangan Vijayanand

La Jolla Institute for Immunology

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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.

Suggested Citation

Meckiff, Benjamin J. and Ramírez-Suástegui, Ciro and Fajardo, Vicente and Chee, Serena J. and Kusnadi, Anthony and Simon, Hayley and Grifoni, Alba and Pelosi, Emanuela and Weiskopf, Daniela and Sette, Alessandro and Ay, Ferhat and Seumois, Grégory and Ottensmeier, Christian and Vijayanand, Pandurangan, Single-Cell Transcriptomic Analysis of SARS-CoV-2 Reactive CD4 + T Cells. Available at SSRN: https://ssrn.com/abstract=3641939 or http://dx.doi.org/10.2139/ssrn.3641939
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Benjamin J. Meckiff

La Jolla Institute for Immunology ( email )

La Jolla, CA
United States

Ciro Ramírez-Suástegui

La Jolla Institute for Immunology ( email )

La Jolla, CA
United States

Vicente Fajardo

La Jolla Institute for Immunology ( email )

La Jolla, CA
United States

Serena J. Chee

University of Southampton - Faculty of Medicine ( email )

Southampton
United Kingdom

Anthony Kusnadi

La Jolla Institute for Immunology ( email )

La Jolla, CA
United States

Hayley Simon

La Jolla Institute for Immunology ( email )

La Jolla, CA
United States

Alba Grifoni

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Emanuela Pelosi

University Hospitals NHS Foundation Trust - Southampton Specialist Virology Center ( email )

Southampton
United Kingdom

Daniela Weiskopf

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Alessandro Sette

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Ferhat Ay

La Jolla Institute for Allergy and Immunology (LIAI)

9420 Athena Cir
La Jolla, CA 92037
United States

University of California, San Diego (UCSD) - School of Medicine

9500 Gilman Drive
MC 0507
La Jolla, CA 92093
United States

Grégory Seumois

La Jolla Institute for Allergy and Immunology (LIAI) - Division of Vaccine Discovery ( email )

La Jolla, CA 92037
United States

Christian Ottensmeier

La Jolla Institute for Immunology

La Jolla, CA
United States

Pandurangan Vijayanand (Contact Author)

La Jolla Institute for Immunology ( email )

La Jolla, CA
United States

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