[PD-1 up-regulation influenced apoptosis of HBV-specific CD8 T cells in patients with acute resolved hepatitis B]

Bin Xu, Zheng Zhang, Ying Shi, Xin-yue Chen, Fu-sheng Wang
Zhonghua Yi Xue za Zhi [Chinese medical journal] 2009 May 5, 89 (17): 1158-61

OBJECTIVE: Programmed death-1 (PD-1) up-regulation can impair virus-specific CD8(+) T-cell responses during chronic viral infection. Whether PD-1 affects virus-specific CD8 T cells in humans with acute hepatitis B virus (HBV) infection remains unknown. This study aimed to characterize the PD-1 expression during acute hepatitis B (AHB), and further addressed how PD-1 regulates the apoptosis of CD8(+) T cells in this disease.

METHODS: PD-1 expression on HBV env-183-191-, env-335-343- and CMV pp65-specific CD8(+) T cells were quantitatively analyzed by flow cytometry in peripheral blood from 15 HLA-A2-positive AHB patients. The spontaneous apoptosis indicated by annexin V expression was performed for analyses of the impact of PD-1 expression. We also confirmed the effects of PD-1/PD-L1 pathway on the in vitro apoptosis of CD8(+) T cells through PD-1 blockade assay.

RESULTS: PD-1 expression on HBV-specific CD8(+) T cells was significantly up-regulated compared with CMV-specific CD8(+) T cells in the early phase of acute HBV infection. High levels of PD-1 expression significantly correlated with the apoptosis of HBV-specific CD8(+) T cells. Blockade of PD-1 ligation using anti-PD-L1 rescued the HepG2.215-induced CD8(+) T cell apoptosis.

CONCLUSION: PD-1/PD-L1 inhibitory pathway is actively involved in the apoptotic regulation of HBV-specific CD8(+) T cells at early phase of acute HBV infection, and high PD-1 expression by HBV-specific CD8(+) T cells appear to efficiently temper liver damage.

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