PD-1 upregulation is associated with HBV-specific T cell dysfunction in chronic hepatitis B patients.
Programmed death-1 (PD-1) is demonstrated to have an increased expression on antigen-specific T cells during chronic virus infections, and the blockage of PD-1/PD-ligand (PD-L1) pathway could restore the function of exhausted T cells. We measured the PD-1 expression levels on HBV-specific CD8 T cells and investigated the role of PD-1/PD-L1 pathway in T-cell responses of patients with different HBV infection statuses. Compared to the patients with convalescent acute hepatitis B, PD-1 expression on total CD8 T cells from chronic hepatitis B (CHB) patients was significantly upregulated, especially on the HBV pentamer-positive CD8 T cells. And PD-L1, but not PD-L2, was also significantly upregulated on PBMC from CHB patients. In CHB patients, HBV-specific T cells and cellular proliferation could be observed under the recombinant HBV-Ag stimulation in vitro, and blockade of PD-1 pathway significantly enhanced the IFN-gamma production and cellular proliferation of PBMC. Furthermore, PD-1 expression level on HBV-pentamers positive CD8 T cells was positively associated with plasma viral load in CHB patients. Thus, PD-1 upregulation on HBV-specific CD8 T cells is engaged in the dysfunction of T cells and high viraemia in CHB patients, and the antiviral T-cell responses could be improved by the blockade of this inhibitory PD-1/PD-L1 pathway.
Peng
Guoping
G
Key Laboratory of Health Ministry, Institute of Infectious Diseases, First Affiliated Hospital, Medical College, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang 310003, China.
Li
Shuping
S
Wu
Wei
W
Tan
Xufei
X
Chen
Yiqiong
Y
Chen
Zhi
Z
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D000998:Antiviral Agents / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D060890:B7-H1 Antigen; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006515:Hepatitis B virus / Q000276:immunology* / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D015854:Up-Regulation; D019562:Viral Load
D015703:Antigens, CD; D000998:Antiviral Agents; D051017:Apoptosis Regulatory Proteins; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D004279:DNA, Viral; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma