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

Lucille Adam (1) , Pierre Rosenbaum (1) , Paul Quentric (1) , Christophe Parizot (1) , Olivia Bonduelle (1) , Noëlline Guillou (1) , Aurélien Corneau (2) , Karim Dorgham (1) , Makoto Miyara (1) , Charles-Edouard Luyt (3) , Amélie Guihot (1) , Guy Gorochov (1) , Christophe Combadière (1) , Behazine Combadière (1)

1 CIMI - Centre d'Immunologie et des Maladies Infectieuses
2 PASS-CYPS - Cytométrie Pitié-Salpêtrière
3 CHU Pitié-Salpêtrière [AP-HP]

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.

Domaines: Immunologie

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, 2021, ⟨10.1172/jci.insight.151571⟩. ⟨hal-03984873v1⟩