PD-1 expression on memory CD8 and CD4 T-cell subsets in healthy humans (43.43)

Abstract

Abstract It has been shown that the PD-1 (programmed death-1) inhibitory pathway is an important regulator of virus-specific CD8 T cell immune responses during a chronic viral infection in mice. Recent reports in HIV-infected people have shown that PD-1 is significantly upregulated on HIV-specific CD8 T cells and these exhausted cells can be reinvigorated by PD-1 blockade. We have tested the profile of PD-1 expression on chronic virus-specific CD8 T cells in normal healthy virus carriers. Analyses of CD8 T-cell subsets revealed that PD-1 was preferentially expressed by effector memory T cells rather than naive or central memory T cells. PD-1 was expressed by most CD8 T cells specific for human chronic infections, such as Epstein-Barr virus and cytomegalovirus, and at a lower level among CD8 T cells specific for infections that are cleared, such as influenza and vaccinia viruses. Blockade of PD-1 signaling using anti-PD-L1 antibody enhanced the ability of virus specific PD-1+ CD8 T cells to proliferate in response to antigen. These data support a role for PD-1 in suppressing CD8 T cells during chronic viral infections in humans. The first two authors contributed equally to this work.