Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19

Naoki Kaneko; Julie Boucau; Hsiao-Hsuan Kuo; Cory Perugino; Vinay S Mahajan; Jocelyn R Farmer; Hang Liu; Thomas J Diefenbach; Alicja Piechocka-Trocha; Kristina Lefteri; Michael T Waring; Katherine R Premo; Bruce D Walker; Jonathan Z Li; Gaurav Gaiha; Xu G Yu; Mathias Lichterfeld; Robert F Padera Jr; Shiv Pillai

doi:10.1016/j.clim.2022.108991

Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19

Clin Immunol. 2022 Apr:237:108991. doi: 10.1016/j.clim.2022.108991. Epub 2022 Mar 29.

Authors

Naoki Kaneko¹, Julie Boucau², Hsiao-Hsuan Kuo², Cory Perugino³, Vinay S Mahajan⁴, Jocelyn R Farmer³, Hang Liu², Thomas J Diefenbach², Alicja Piechocka-Trocha⁵, Kristina Lefteri², Michael T Waring², Katherine R Premo², Bruce D Walker⁶, Jonathan Z Li⁷, Gaurav Gaiha⁸, Xu G Yu², Mathias Lichterfeld⁹, Robert F Padera Jr¹⁰, Shiv Pillai¹¹

Affiliations

¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
² Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
³ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Rheumatology Allergy and Immunology, Massachusetts General Hospital, Boston, MA 02114, USA.
⁴ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁵ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA.
⁶ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD, 20815, USA; Department of Biology and Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁸ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
⁹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
¹⁰ Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: rpadera@rics.bwh.harvard.edu.
¹¹ Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA. Electronic address: pillai@helix.mgh.harvard.edu.

Abstract

Many studies have been performed in severe COVID-19 on immune cells in the circulation and on cells obtained by bronchoalveolar lavage. Most studies have tended to provide relative information rather than a quantitative view, and it is a combination of approaches by various groups that is helping the field build a picture of the mechanisms that drive severe lung disease. Approaches employed to date have not revealed information on lung parenchymal T cell subsets in severe COVID-19. Therefore, we sought to examine early and late T cell subset alterations in the lungs and draining lymph nodes in severe COVID-19 using a rapid autopsy protocol and quantitative imaging approaches. Here, we have established that cytotoxic CD4+ T cells (CD4 + CTLs) increase in the lungs, draining lymph nodes and blood as COVID-19 progresses. CD4 + CTLs are prominently expanded in the lung parenchyma in severe COVID-19. In contrast CD8+ T cells are not prominent, exhibit increased PD-1 expression, and no obvious increase is seen in the number of Granzyme B+ CD8+ T cells in the lung parenchyma in severe COVID-19. Based on quantitative evidence for re-activation in the lung milieu, CD4 + CTLs may be 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.

Keywords: CD8+ T cells; COVID-19; Cytotoxic CD4+ T cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes*
CD8-Positive T-Lymphocytes
COVID-19*
Humans
Lung
T-Lymphocyte Subsets
T-Lymphocytes, Cytotoxic

Grants and funding

U19 AI110495/AI/NIAID NIH HHS/United States