Cutting Edge: Programmed Death-1 Up-Regulation Is Involved in the Attrition of Cytomegalovirus-Specific CD8+ T Cells in Acute Self-Limited Hepatitis B Virus Infection

Abstract

Attrition of heterologous virus-specific CD8+ T cells has been demonstrated in murine viral infection; however, little is known regarding this phenomenon in human viral infections. In this study, we observed that CMV-specific CD8+ T cells displayed numerical decline and functional impairment in the early phase of acute infection, whereas programmed death-1 (PD-1) expression was significantly up-regulated by these CMV-specific CD8+ T cells. This early PD-1 up-regulation was found to be closely associated with the increased apoptotic sensitivity of CMV-specific CD8+ T cells. The in vitro addition of anti-PD-1 further enhanced the spontaneous apoptosis of CMV-specific CD8+ T cells; however, blockade of the PD-1-mediated pathway with anti-PD-L1 significantly restored the CMV-specific CD8+ T cell proliferation and IFN-γ production. Thus, PD-1 plays a crucial role in the attrition of CMV-specific CD8+ T cells in acute hepatitis B virus infection, which in turn, influences the preexisting homeostatic virus-specific CD8+ T cell pool.