PD-L1 mediated T cell inhibition by regulatory plasma cells induced after sepsis and COVID-19

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 + B220 Low CD138 + 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 IFNɣ 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.