The Associativity Between Programmed-death-1(PD-1) And The Progression Of Acute Hepatitis B

Objective Programmed death-1(PD-1) up-regulation impairs virus-specific CD8~+ T-cell responses during chronic viral infection.Whether PD-1 affects virus-specific CD8~+ T cells in humans with acute viral infection remain largely undefined.This study aimed to characterize the PD-1 expression during acute hepatitis B(AHB),and address the associativity between the PD-1 dynamics and memory T-cell formation during acute HBV infection.Further more,we investigate how the PD-1 regulates antiviral immunity in acute HBV infection.Methods HBV-specific CD8~+ T cells in peripheral blood from 16 HLA-A2-positive AHB patients at the clinical onset were quantitatively analyzed and PD-1 expression on HBV-specific CD8~+ T cells were measured using flow cytometry.Serum ALT levels,HBV markers and HBV-DNA levels were evaluated for each subject.Proliferation and intracellular IFN-γstaining was performed for analyses of the impact of PD-1 expression,even when the PD-1/PD-L1 interactions was blocked in vitro.Peripheral HBV-specific CD8~+ T cells from 18 HLA-A2-positive AHB patients were longitudinally quantitatively analyzed,and PD-1,memory marker CCR7,CD45RA and CD127 and activation marker CD38 on HBV-specific CD8~+ T cells were measured using flow cytometry.Results All 16 AHB patients examined had multiple pentamer responses in the early phase of infection.Blockade of PD-1 ligation enhances the amount of IFN-γproduction by HBV-specific CD8~+ T cells following 6-h stimulation with cognate peptide.18 AHB patients were followed-up for 8-32 weeks.We found that PD-1 was significantly up-regulated at clinical onset.PD-1 up-regulation favers the apoptosis of HBV-specific CD8~+ T cells during the early phase of acute HBVinfection.And PD-1 reduction was correlated with the increased funtion of HBV-specific CD8~+ T cells after disease resolution in AHB patients. Following disease resolution and HBsAg loss,the dynamic decrease in PD-1 expression was found to correlate with the phenotypic development of memory CD8~+ T cells,indicating by the increases of CCR7,CD45RA and CD127,and decrease in CD38 which prompt the memory T lymphocytes emerged.Conclusions PD-1/PD-L1 pathway plays a role in the regulation of the function of HBV-specific CD8~+ T cells at early phase of acute HBV infection and high PD-1 expression by HBV-specific CD8~+ T cells,whose ability of IFN-γproduction was effectively inhibited,appear to efficiently temper liver damage.PD-1-mediated negative signaling may be closely associated with memory T-cell formation during acute HBV infection.