SARS-CoV-2-Specific T Cells Exhibit Phenotypic Features of Helper Function, Lack of Terminal Differentiation, and High Proliferation Potential

• Type of Material: Article
• Authors: Jason Neidleman, Gladstone Institute of Cardiovascular Disease; Xiaoyu Luo, Gladstone Institute of Cardiovascular Disease; Julie Frouard, Gladstone Institute of Cardiovascular Disease; Guorui Xie, Gladstone Institute of Cardiovascular Disease; Gurjot Gill, University of California San Francisco; Ellen S. Stein, University of California San Francisco; Matthew McGregor, Gladstone Institute of Cardiovascular Disease; Tongcui Ma, Gladstone Institute of Cardiovascular Disease; Ashley F. George, Gladstone Institute of Cardiovascular Disease; Astrid Kosters, Emory University; Warner C. Greene, Gladstone Institute of Cardiovascular Disease; Joshua Vasquez, University of California San Francisco; Eliver Ghosn, Emory University; Sulggi Lee, Zuckerberg San Francisco General Hospital; Nadia R. Roan, Gladstone Institute of Cardiovascular Disease
• Language: English
• Date: 2020-09-22
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.xcrm.2020.100081
• Title of Journal or Parent Work: CELL REPORTS MEDICINE
• Volume: 1
• Issue: 6
• Start Page: 100081
• End Page: 100081
• Grant/Funding Information: This work was supported by the Van Auken Private Foundation and David Henke; the Program for Breakthrough Biomedical Research, which is partly funded by the Sandler Foundation; and philanthropic funds donated to the Gladstone Institutes by The Roddenberry Foundation and individual donors devoted to COVID-19 research. We acknowledge NIH DRC Center grant P30 DK063720 and S10 1S10OD018040-01 for use of the CyTOF instrument. We also thank Stanley Tamaki, Tomoko Kakegawa Peech, and Caudia Bispo for CyTOF assistance at the Parnassus Flow Core; Nicole Lazarus and Eugene Butcher for the Act1 antibody; Françoise Chanut for editorial assistance; and Robin Givens for administrative assistance.
• Keywords: Research & Experimental Medicine; ACUTE RESPIRATORY SYNDROME; RESPONSES; CYTOMETRIC ANALYSIS; CXC CHEMOKINE RECEPTOR-5; CD8(+); SARS CORONAVIRUS; EXPRESSION; CD4(+); IMMUNE; CYTOMEGALOVIRUS; Life Sciences & Biomedicine; Science & Technology; Medicine, Research & Experimental; Cell Biology
• Research Categories: Biology, Virology; Biology, Cell

Abstract

Convalescing coronavirus disease 2019 (COVID-19) patients mount robust T cell responses against SARS-CoV-2, suggesting an important role of T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from nine individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells and predominantly Tcm cells with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly Temra cells in a state of less terminal differentiation than most Temra cells. Subsets of SARS-CoV-2-specific T cells express CD127, can proliferate homeostatically, and can persist for over 2 months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection and support an important role of SARS-CoV-2-specific T cells in host control of COVID-19. Combining CyTOF with single-cell detection of antigen-specific cells, Neidleman et al. provide an in-depth view of the phenotypic features of CD4+ and CD8+ T cells recognizing SARS-CoV-2 epitopes. These cells are different from T cells recognizing CMV, harbor diverse homing properties and effector functions, and include CD127-expressing cells.