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Nucleocapsid-specific and PD-L1+CXCR3+ CD8 polyfunctional T-cell abundances are associated with survival of critical SARS-CoV2-infected patients

Abstract : Rationale. The importance of the adaptative T cell response in the control and resolution of viral infection has been well-established. However, the nature of T cell-mediated viral control mechanisms in life-threatening stages of COVID-19 has yet to be determined. Objective. The aim of the present study was to determine the function and phenotype of T cell populations associated with survival or death of COVID-19 patients under intensive care as a result of phenotypic and functional profiling by mass cytometry. Findings. Increased frequencies of circulating, polyfunctional, CD4+CXCR5+HLA-DR+ stem cell memory T cells (TSCM) and decreased proportions of Granzyme-B and Perforin-expressing effector memory T cells (TEM) were detected in recovered and deceased patients, respectively. The higher abundance of polyfunctional CD8+PD-L1+CXCR3+ T effector cells, CXCR5+HLA-DR+ TSCM, as well as anti-nucleocapsid (NC) cytokine-producing T cells permitted to differentiate between recovered and deceased patients. The results from a principal component analysis showed an imbalance in the T cell compartment allowed for the separation of recovered and deceased patients. The paucity of circulating CD8+PD-L1+CXCR3+ Teff-cells and NC-specific CD8+ T-cells accurately forecasts fatal disease outcome. Conclusion. This study provides insight into the nature of the T cell populations involved in the control of COVID-19 and therefor might impact T cell-based vaccine designs for this infectious disease.
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https://hal.sorbonne-universite.fr/hal-03294164
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Submitted on : Wednesday, July 21, 2021 - 2:30:55 PM
Last modification on : Friday, May 20, 2022 - 11:06:35 AM
Long-term archiving on: : Friday, October 22, 2021 - 6:39:34 PM

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Lucille Adam, Pierre Rosenbaum, Paul Quentric, Christophe Parizot, Olivia Bonduelle, et al.. Nucleocapsid-specific and PD-L1+CXCR3+ CD8 polyfunctional T-cell abundances are associated with survival of critical SARS-CoV2-infected patients. JCI Insight, American Society for Clinical Investigation, 2021, ⟨10.1172/jci.insight.151571⟩. ⟨hal-03294164⟩

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