PD-L1 costimulation of the CD8 T cell response to Listeria monocytogenes infection (63.16)

Abstract

Abstract It is well known that programmed death ligand-1 (PD-L1) transduces a suppressive signal, increasing the activation threshold of T cells via its counterreceptors PD1 and CD80 (B7.1). On the other hand, other studies have suggested a possible role of PD-L1 as costimulator. In this study, we analyzed the role of PD-L1 in the primary CD8 T cell response to Listeria monocytogenes infection. PD-L1 blockade using the monoclonal antibody (mAb) 10F.9G2 impaired antigen-specific CD8 effector T cell expansion, particularly limiting short-lived effector cell differentiation. Simultaneous CD4 T cell depletion and anti-PD-L1 blockade exacerbated the effect of either treatment alone demonstrating that PD-L1 provides important costimulation even in the absence of CD4 T cells. Most importantly, specific blockade of PD-L1 binding to CD80 (43H12 mAb) or PD-1 (RPM1-14 mAb) during Listeria monocytogenes infection did not recapitulate blockade with 10F.9G2. These data suggest a 3rd unknown binding partner for PD-L1 that is responsible for positive costimulation of antigen-specific CD8 effector T cells. We conclude that PD-L1 plays an important role in antigen-specific CD8 effector T cells during Listeria monocytogenes infection through a novel costimulatory pathway.