Intrahepatic PD-1/PD-L1 up-regulation closely correlates with inflammation and virus replication in patients with chronic HBV infection.
Chronic hepatitis B was characterized by fluctuant immune response to infected hepatocytes resulting in hepatic inflammation and virus persistence. Recently, Programmed Death-1 (PD-1) and its ligand PD-L1 have been demonstrated to play an essential role in balancing antiviral immunity and inflammation in the livers of acute hepatitis B patients, significantly influencing disease outcome. PD-1 up-regulation in peripheral T cells is associated with immune dysfunction in chronic hepatitis B patients. However, the effect of PD-1/PD-L1 on hepatic damage and chronic infective status is still unknown in patients with chronic HBV infection. Here, we report up-regulation of PD-1 and PD-L1 in liver biopsies from 32 chronic HBV patients compared to 4 healthy donors. PD-1/PD-L1 up-regulation was significantly associated with hepatic inflammation and ALT elevation. Moreover, appropriate up-regulation but not overexpression of PD-L1 in the active phase of chronic hepatitis B as well as lower expression of PD-L1 in the inactive phase in liver residential antigen presenting cells (including Kupffer cells and sinusoidal endothelial cells) may contribute to viral inhibition. Our data suggest that the intrahepatic interaction of PD-1 and PD-L1 might play an important role in balancing the immune response to HBV and immune-mediated liver damage in chronic HBV infection.
Xie
Zhunyi
Z
Laboratory of Immunoregulation, Institute of Immunology, PLA, Third Military Medical University, Chongqing, PR China.
Chen
Yongwen
Y
Zhao
Songtao
S
Yang
Zhiqing
Z
Yao
Xiaohong
X
Guo
Sheng
S
Yang
Chengying
C
Fei
Lei
L
Zeng
Xingguang
X
Ni
Bing
B
Wu
Yuzhang
Y
D000328:Adult; D000938:Antigen-Presenting Cells / Q000378:metabolism / Q000473:pathology; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D060890:B7-H1 Antigen; D005260:Female; D005455:Fluorescent Antibody Technique; D006515:Hepatitis B virus / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D061026:Programmed Cell Death 1 Receptor; D015854:Up-Regulation; D019562:Viral Load; D014779:Virus Replication
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor