PD-1 upregulation is associated with HBV-specific T cell dysfunction in chronic hepatitis B patients

Mol Immunol. 2008 Feb;45(4):963-70. doi: 10.1016/j.molimm.2007.07.038. Epub 2007 Sep 14.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / biosynthesis*
  • Antiviral Agents / therapeutic use
  • Apoptosis Regulatory Proteins / antagonists & inhibitors
  • Apoptosis Regulatory Proteins / biosynthesis*
  • B7-H1 Antigen
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • DNA, Viral / blood
  • Female
  • Hepatitis B virus / immunology*
  • Hepatitis B virus / metabolism
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / immunology*
  • Hepatitis B, Chronic / microbiology
  • Humans
  • Interferon-gamma / biosynthesis
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor
  • Up-Regulation
  • Viral Load


  • Antigens, CD
  • Antiviral Agents
  • Apoptosis Regulatory Proteins
  • B7-H1 Antigen
  • CD274 protein, human
  • DNA, Viral
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Interferon-gamma