Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients

• Published in: The Journal of experimental medicine 2020-12, Vol.217 (12)
• Main Authors: Jouan, Youenn, Guillon, Antoine, Gonzalez, Loïc, Perez, Yonatan, Boisseau, Chloé, Ehrmann, Stephan, Ferreira, Marion, Daix, Thomas, Jeannet, Robin, François, Bruno, Dequin, Pierre-François, Si-Tahar, Mustapha, Baranek, Thomas, Paget, Christophe
• Format: Article
• Language: English
• Subjects: Aged; Antigens, CD - blood; Antigens, Differentiation, T-Lymphocyte - blood; Betacoronavirus - genetics; Brief Definitive Report; Cells, Cultured; Coronavirus Infections - immunology; Coronavirus Infections - virology; COVID-19; Cytokines - metabolism; Female; Humans; Infectious Disease and Host Defense; Inflammation - immunology; Inflammation - metabolism; Innate Immunity and Inflammation; Lectins, C-Type - blood; Life Sciences; Male; Middle Aged; Mucosal Immunology; Mucosal-Associated Invariant T Cells - immunology; Mucosal-Associated Invariant T Cells - metabolism; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; Pandemics; Phenotype; Pneumonia, Viral - immunology; Pneumonia, Viral - virology; Prognosis; Prospective Studies; Receptors, Antigen, T-Cell, gamma-delta - metabolism; Respiratory Distress Syndrome - immunology; Respiratory Distress Syndrome - virology; SARS-CoV-2; Severity of Illness Index
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20200872

COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19-driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS-CoV-2-driven ARDS.