PD-1/PD-L1 signal pathway participates in HCV F protein-induced T cell dysfunction in chronic HCV infection.
Programmed cell death-1/programmed cell death-1 ligand 1 (PD-1/PD-L1) inhibitory signal pathway has been verified to be involved in the establishment of persistent viral infections. Blockade of PD-1/PD-L1 engagement to reinvigorate T cell activity is supposed to be a potential therapeutic scheme. Studies have verified the participation of PD-1/PD-L1 in hepatitis C virus (HCV) core protein-regulated immune response. To determine the roles of PD-1/PD-L1 signal pathway in HCV F protein-induced immunoreaction in chronic HCV infection, variations in T cells were examined. The results showed that PD-1 expression on CD8(+) and CD4(+) T cells was increased with HCV F stimulation in both chronic HCV patients and healthy controls, and could be reduced partly by PD-1/PD-L1 blocking. Additionally, by PD-1/PD-L1 blocking, HCV F-induced inhibition of T cell proliferation and promotion of cellular apoptosis were partly or even totally recovered. Furthermore, levels of both Th1 and Th2 cytokines were elevated in the presence of anti-PD-L1 antibody. All these results indicated that PD-1/PD-L1 signal pathway also participates in HCV F protein-induced immunoregulation. PD-1/PD-L1 blocking plays important roles in the restoration of effective functionality of the impaired T cells in chronic HCV patients.
School of Life Science and Technology, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, 210009, Jiangsu, China.
Wen
W
Xiao
Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210002, China. phoenix0929@126.com.
Long Feng
LF
Jiang
School of Life Science and Technology, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, 210009, Jiangsu, China. xiaozhaodeng2014@163.com.|Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China. xiaozhaodeng2014@163.com.
Xiao Zhao
XZ
Deng
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
Dan Yan
DY
Zhu
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
Jia Ping
JP
Pei
School of Life Science and Technology, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, 210009, Jiangsu, China.
Mao Lei
ML
Xu
Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China.
Bing Jun
BJ
Li
Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China.
Chang Jun
CJ
Wang
Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China.
Jing Hai
JH
Zhang
Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China.
Qi
Q
Zhang
Department of Clinical Laboratory, Nanjing Second Hospital, Nanjing, China.
Zhen Xian
ZX
Zhou
Department of Clinical Laboratory, Yixing People's Hospital, Yixing, China.
Wei Liang
WL
Ding
Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China.
Xiao Dong
XD
Xu
School of Life Science and Technology, China Pharmaceutical University, No. 24, Tongjiaxiang, Nanjing, 210009, Jiangsu, China.
Ming
M
Yue
D000328:Adult; D017209:Apoptosis / Q000235:genetics; D060890:B7-H1 Antigen / Q000378:metabolism*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006508:Hepatitis Antibodies; D019698:Hepatitis C, Chronic / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014758:Viral Core Proteins / Q000276:immunology*
D060890:B7-H1 Antigen; D016207:Cytokines; D006508:Hepatitis Antibodies; D061026:Programmed Cell Death 1 Receptor; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus
HCV F protein; Hepatitis C virus (HCV); PD-1/PD-L1; Restoration; T cell exhaustion