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Inhibition of viral replication downregulates CD4(+)CD25(high) regulatory T cells and programmed death-ligand 1 in chronic hepatitis B.

Abstract
Chronic hepatitis B is characterized by an impaired immune response to hepatitis B virus (HBV). Telbivudine treatment has significantly improved the clinical outcome of chronic HBV infection. However, the underlying mechanism behind the antiviral response of patients treated with nucleoside analogs remains unclear. To gather more evidence about the mechanism responsible for the weak immune response, in this study we analyzed the effects on HBV viral load of treatment with the nucleoside analogue telbivudine and the percentage of Tregs, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, and related cytokine production. Peripheral blood mononuclear cells (PBMCs) and serum of 28 patients with chronic hepatitis B were collected at baseline, and 3 mo and 6 mo after therapy was begun. In parallel with the decline in viral load and serum ALT normalization, we found a decline in circulating CD4(+)CD25(high) Tregs, PD-L1 on CD4(+) T cells, and IL-9 production. The expression of PD-1 on CD4(+) T cells and the production of IFN-γ did not increase during therapy. Our findings suggest that the antiviral effect of the nucleoside analogs may be attributable not only to their direct effect on virus suppression, but also to their immunoregulatory capabilities.
AuthorsXue-Ping Nan, Ye Zhang, Hai-Tao Yu, Rui-Lin Sun, Mei-Juan Peng, Yu Li, Wen-Jing Su, Jian-Qi Lian, Jiu-Ping Wang, Xue-Fan Bai
JournalViral immunology (Viral Immunol) Vol. 25 Issue 1 Pg. 21-8 (Feb 2012) ISSN: 1557-8976 [Electronic] United States
PMID22233255 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiviral Agents
  • B7-H1 Antigen
  • CD274 protein, human
  • Cytokines
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-9
  • Nucleosides
  • Pyrimidinones
  • Telbivudine
  • Thymidine
Topics
  • Adult
  • Antiviral Agents (pharmacology, therapeutic use)
  • B7-H1 Antigen (genetics, metabolism)
  • CD4-Positive T-Lymphocytes (immunology)
  • Cytokines (metabolism)
  • Down-Regulation
  • Female
  • Hepatitis B virus (drug effects, physiology)
  • Hepatitis B, Chronic (drug therapy, immunology, virology)
  • Humans
  • Interleukin-2 Receptor alpha Subunit (metabolism)
  • Interleukin-9 (metabolism)
  • Lymphocyte Count
  • Male
  • Nucleosides (pharmacology, therapeutic use)
  • Pyrimidinones (pharmacology, therapeutic use)
  • T-Lymphocytes, Regulatory (drug effects, immunology, metabolism, virology)
  • Telbivudine
  • Thymidine (analogs & derivatives)
  • Treatment Outcome
  • Viral Load (drug effects)
  • Virus Replication (drug effects)

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