학술논문
T cell apoptosis characterizes severe Covid-19 disease
Document Type
Article
Author
André, Sonia; Picard, Morgane; Cezar, Renaud; Roux-Dalvai, Florence; Alleaume-Butaux, Aurélie; Soundaramourty, Calaiselvy; Cruz, André Santa; Mendes-Frias, Ana; Gotti, Clarisse; Leclercq, Mickaël; Nicolas, Alexandre; Tauzin, Alexandra; Carvalho, Alexandre; Capela, Carlos; Pedrosa, Jorge; Castro, António Gil; Kundura, Lucy; Loubet, Paul; Sotto, Albert; Muller, Laurent; Lefrant, Jean-Yves; Roger, Claire; Claret, Pierre-Géraud; Duvnjak, Sandra; Tran, Tu-Anh; Racine, Gina; Zghidi-Abouzid, Ouafa; Nioche, Pierre; Silvestre, Ricardo; Droit, Arnaud; Mammano, Fabrizio; Corbeau, Pierre; Estaquier, Jérôme
Source
Cell Death and Differentiation; August 2022, Vol. 29 Issue: 8 p1486-1499, 14p
Subject
Language
ISSN
13509047; 14765403
Abstract
Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.