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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 Infection¹

Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, China

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- 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.

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¹ This study was supported by National Key Basic Research Program of China Grants 2007CB512805 and 2006CB504305 and National Science Fund for Distinguished Young Scholars Grant 30525042.

² J.-Y.Z. and Z.Z. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Fu-Sheng Wang, Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China. E-mail address: fswang{at}public.bta.net.cn

⁴ Abbreviations used in this paper: PD-1, programmed death-1; AHB, acute hepatitis B; HBV, hepatitis B virus; HC, healthy control; HBsAg, hepatitis B surface antigen; PD-L1, PD-1 ligand.