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


CONCLUSIONS
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.
Xu
Bin
B
Department of Infections Diseases, Beijing Youan Hospital, Affiliated of Capital University of Medical Science, Beijing 100069, China.
Zhang
Zheng
Z
Shi
Ying
Y
Chen
Xin-yue
XY
Wang
Fu-sheng
FS
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D004279:DNA, Viral; D005260:Female; D006509:Hepatitis B / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D015854:Up-Regulation; D055815:Young Adult
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor