T cell apoptosis characterizes severe Covid-19 disease.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.