PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing

Cytotoxic cd8+ t lymphocytes (ctl) efficiently control acute virus infections but can become exhausted when a chronic infection develops. signaling of the inhibitory receptor pd-1 is an important mechanism for the development of virus-specific cd8+ t cell dysfunction. however,it has recently been shown that during the initial phase of infection virus-specific cd8+ t cells express high levels of pd-1,but are fully competent in producing cytokines and killing virus-infected target cells. to better understand the role of the pd-1 signaling pathway in cd8+ t cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by ctls. we observed increased levels of pd-l1 expression after infection of cells with the murine friend retrovirus (fv) or with hiv. in fv infected mice,virus-specific ctls efficiently eliminated infected target cells that expressed low levels of pd-l1 or that were deficient for pd-l1 but the population of pd-l1high cells escaped elimination and formed a reservoir for chronic fv replication. infected cells with high pd-l1 expression mediated a negative feedback on cd8+ t cells and inhibited their expansion and cytotoxic functions. these findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on pd-l1 expression levels on virus infected target cells. © 2015 akhmetzyanova et al.