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Expansion of Cytotoxic CD4+ T Cells in the Lungs in Severe COVID-19

46 Pages Posted: 26 Mar 2021 Publication Status: Review Complete

See all articles by Naoki Kaneko

Naoki Kaneko

Ragon Institute of MGH, MIT and Harvard

Julie Boucau

Ragon Institute of MGH, MIT and Harvard

Hsiao-Hsuan Kuo

Ragon Institute of MGH, MIT and Harvard

Cory Perugino

Ragon Institute of MGH, MIT and Harvard

Vinay S. Mahajan

Ragon Institute of MGH, MIT and Harvard

Jocelyn R. Farmer

Ragon Institute of MGH, MIT and Harvard

Hang Liu

Ragon Institute of MGH, MIT and Harvard

Thomas J. Diefenbach

Ragon Institute of MGH, MIT and Harvard

Alicja Piechocka-Trocha

Ragon Institute of MGH, MIT and Harvard

Kristina Lefteri

Ragon Institute of MGH, MIT and Harvard

Michael T. Waring

Ragon Institute of MGH, MIT and Harvard

Katherine R. Premo

Ragon Institute of MGH, MIT and Harvard

Bruce D. Walker

Ragon Institute of MGH, MIT and Harvard; Howard Hughes Medical Institute (HHMI) - Chevy Chase; Massachusetts Institute of Technology (MIT) - Institute for Medical Engineering and Science

Jonathan Z. Li

Brigham and Women's Hospital - Department of Medicine

Gaurav Gaiha

Ragon Institute of MGH, MIT and Harvard

Xu Yu

Ragon Institute of MGH, MIT and Harvard

Matthias Lichterfeld

Ragon Institute of MGH, MIT and Harvard

Robert F. Padera

Brigham and Women's Hospital - Department of Pathology

Shiv Pillai

Ragon Institute of MGH, MIT and Harvard

More...

Abstract

The contributions of T cells infiltrating the lungs to SARS-CoV-2 clearance and disease progression are poorly understood.  Although studies of CD8+ T cells in bronchoalveolar lavage and blood have suggested that these cells are exhausted in severe COVID-19, CD4+ T cells have not been systematically interrogated within the lung parenchyma. We establish here that cytotoxic CD4+ T cells (CD4+CTLs) are prominently expanded in the COVID-19 lung infiltrate. CD4+CTL numbers in the lung increase with disease severity and progression is accompanied by widespread HLA-DR expression on lung epithelial and endothelial cells, increased apoptosis of epithelial cells and tissue remodeling. Based on quantitative evidence for re-activation in the lung milieu, CD4+ CTLs are as likely to drive viral clearance as CD8+ T cells and may also be contributors to lung inflammation and eventually to fibrosis in severe COVID-19.

Funding: This work was supported by NIH U19 AI110495 to SP. Funding for these studies from the Massachusetts Consortium of Pathogen Readiness, the Mark and Lisa Schwartz Foundation and Enid Schwartz is also acknowledged.

Declaration of Interest: None to declare.

Ethical Approval: This study was performed with the approval of the Institutional Review Boards at the Massachusetts General Hospital and the Brigham and Women’s Hospital.

Suggested Citation

Kaneko, Naoki and Boucau, Julie and Kuo, Hsiao-Hsuan and Perugino, Cory and Mahajan, Vinay S. and Farmer, Jocelyn R. and Liu, Hang and Diefenbach, Thomas J. and Piechocka-Trocha, Alicja and Lefteri, Kristina and Waring, Michael T. and Premo, Katherine R. and Walker, Bruce D. and Li, Jonathan Z. and Gaiha, Gaurav and Yu, Xu and Lichterfeld, Matthias and Padera, Robert F. and Pillai, Shiv, Expansion of Cytotoxic CD4+ T Cells in the Lungs in Severe COVID-19. Available at SSRN: https://ssrn.com/abstract=3813278 or http://dx.doi.org/10.2139/ssrn.3813278
This version of the paper has not been formally peer reviewed.

Naoki Kaneko

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Julie Boucau

Ragon Institute of MGH, MIT and Harvard

Boston, MA
United States

Hsiao-Hsuan Kuo

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Cory Perugino

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Vinay S. Mahajan

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Jocelyn R. Farmer

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Hang Liu

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Thomas J. Diefenbach

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Alicja Piechocka-Trocha

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Kristina Lefteri

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Michael T. Waring

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Katherine R. Premo

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Bruce D. Walker

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Howard Hughes Medical Institute (HHMI) - Chevy Chase ( email )

4000 Jones Bridge Road
Chevy Chase, MD 20815-6789
United States

Massachusetts Institute of Technology (MIT) - Institute for Medical Engineering and Science ( email )

Cambridge, MA
United States

Jonathan Z. Li

Brigham and Women's Hospital - Department of Medicine ( email )

Boston, MA 02115
United States

Gaurav Gaiha

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Xu Yu

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Matthias Lichterfeld

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Robert F. Padera

Brigham and Women's Hospital - Department of Pathology ( email )

75 Francis St.
Boston, MA 02115
United States

Shiv Pillai (Contact Author)

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

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