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


CONCLUSIONS
PD-1-mediated negative signaling may be closely associated with memory T-cell formation during acute self-limited hepatitis B.
Gu
Lan-lan
LL
Institute of Mincrobiology Chinese Academy of Sciences, Beijing 100101, China.
Xu
Bin
B
Zhang
Ji-yuan
JY
Zhang
Zheng
Z
Wang
Fu-sheng
FS
D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor