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Journal Articles Cell Death and Differentiation Year : 2022

T cell apoptosis characterizes severe Covid-19 disease

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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.
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Origin : Publication funded by an institution

Dates and versions

inserm-03738821 , version 1 (26-07-2022)

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Sonia André, Morgane Picard, Renaud Cezar, Florence Roux-Dalvai, Aurélie Alleaume-Butaux, et al.. T cell apoptosis characterizes severe Covid-19 disease. Cell Death and Differentiation, 2022, Online ahead of print. ⟨10.1038/s41418-022-00936-x⟩. ⟨inserm-03738821⟩
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