[Dynamic expression of PD-1 in HBV-specific cytotoxic T lymphocytes correlates with memory T-cell development in acute hepatitis B patients]

Lan-lan Gu, Bin Xu, Ji-yuan Zhang, Zheng Zhang, Fu-sheng Wang
Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology 2008, 16 (9): 649-53

OBJECTIVES: Programmed death-1 (PD-1) up-regulation impairs virus-specific CD8+ T-cell responses during chronic viral infection. Whether PD-1 expression influences the virus-specific CD8+ T cells in humans with acute viral infection remains largely undefined. This study aims to characterize the PD-1 expression during acute hepatitis B (AHB), and further addresses the association between the PD-1 dynamics and memory T-cell formation during acute HBV infection.

METHODS: Peripheral HBV-specific CD8+ T cells from 11 HLA-A2-positive AHB patients were longitudinally quantitatively analyzed, and PD-1, memory markers CCR7, CD45RA and CD127 and activation marker CD38 on HBV-specific CD8+ T cells were measured using flow cytometric assay. Serum ALT, HBsAg, HBsAb and HBV-DNA levels were evaluated for each subject.

RESULTS: All 11 AHB patients examined had multiple pentamer-positive CD8+ T-cell responses in their early phase of HBV infection. Specifically, their PD-1 on pentamer-positive CD8+ T-cells was significantly up-regulated at the onset of their disease. Following their disease resolution, the dynamic decrease in PD-1 expression was found to correlate with the phenotypic development of memory CD8+ T cells, indicated by the increases in CCR7, CD45RA and CD127 and decrease in CD38.

CONCLUSION: PD-1-mediated negative signaling may be closely associated with memory T-cell formation during acute self-limited hepatitis B.

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