PD-L1 mediated T cell inhibition by regulatory plasma cells induced after sepsis and COVID-19
Gossez, M.; Vigneron, C.; Vandermoeten, A.; Lepage, M.; Courcol, L.; Coudereau, R.; Paidassi, H.; Jallades, L.; Lopez, J.; Kandara, K.; Ortillon, M.; Mommert, M.; Fabri, A.; Peronnet, E.; Grosjean, C.; Buisson, M.; Lukaszewicz, A.-C.; Rimmele, T.; Argaud, L.; Cour, M.; Py, B. F.; Thaunat, O.; Defrance, T.; monneret, g.; VENET, F.
Show abstract
A better understanding of sepsis-induced immunosuppression pathophysiology is desirable for the development of novel therapeutic strategies to prevent and reduce the rates of secondary infections and their associated mortality. Here we demonstrate that PD-L1+CD44+B220LowCD138+IgM+ regulatory plasma cells (PCs) are induced in a murine model of sepsis-induced immune alterations and in critically ill patients with bacterial sepsis and COVID-19. This was revealed both by detailed analysis of their phenotypical features and gene expression profile and by functional explorations comparing capacity of purified B cells and PCs to suppress T cell proliferation and IFN{gamma} secretion ex vivo. Sepsis-induced regulatory PCs exerted their suppressive function on T cells through IL-10 production and increased PD-L1 expression independently of regulatory T cells. Our findings thus reveal a novel pathophysiological mechanism of sepsis-induced immunosuppression that involves regulatory PCs. As such, these PCs constitute valid therapeutic targets to improve immune cell functions impaired by sepsis.
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