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.
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-gamma 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.
Zhang
Ji-Yuan
JY
Research Center for Biological Therapy, Beijing 302 Hospital, Beijing, China.
Zhang
Zheng
Z
Jin
Bo
B
Zhang
Shu-Ye
SY
Zhou
Chun-Bao
CB
Fu
Jun-Liang
JL
Wang
Fu-Sheng
FS