Dynamic decrease in PD-1 expression correlates with HBV-specific memory CD8 T-cell development in acute self-limited hepatitis B patients

Zheng Zhang, Bo Jin, Ji-Yuan Zhang, Bin Xu, Huifen Wang, Ming Shi, E John Wherry, George K K Lau, Fu-Sheng Wang
Journal of Hepatology 2009, 50 (6): 1163-73

BACKGROUND/AIMS: Programmed death-1 (PD-1) upregulation can impair virus-specific CD8 T-cell responses during chronic viral infection. Whether and how PD-1 affects virus-specific memory CD8 T cells in humans with acute viral infection, however, remains largely undefined.

METHODS: The association between PD-1 expression and HBV-specific memory CD8 T-cell responses were longitudinally analyzed in eighteen patients with acute hepatitis B virus (HBV) infection, including ten patients with human leucocyte antigen (HLA)-A201 and eight with other HLA-A2 subtypes.

RESULTS: At clinical onset, PD-1 was significantly up-regulated and subsequently led to the functional suppression of HBV-specific effector CD8 T cells, as blocking PD-1/PD-L1 interactions in vitro enhanced their proliferation and IFN-gamma production. Following disease resolution, HBV-specific effector CD8 T cells developed into memory T cells. During this period, the dynamic PD-1 decrease was numerically correlated with the reduction of HBV-specific CD8 T-cell frequency, phenotypically with an acquisition of CCR7, CD45RA and CD127 expressions, and functionally with the increase in proliferation and IFN-gamma production of the memory T cells.

CONCLUSIONS: PD-1-mediated inhibitory signaling not only attenuates HBV-specific CD8 T-cell effector function during the acute phase of infection but also correlates with the development of HBV-specific memory CD8 T cells following disease resolution.

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