title: Inhibition of viral replication reduces regulatory T cells and enhances the antiviral immune response in chronic hepatitis B.
abstract: Regulatory T cells (Treg) play a key role in the impaired immune response that is typical for a chronic Hepatitis B virus (HBV) infection. To gain more insight in the mechanism that is responsible for this impaired immune response, the effect of viral load reduction resulting from treatment with the nucleotide analogue adefovir dipivoxil on the percentages of Treg and HBV-specific T-cell responses was analyzed. Peripheral blood mononuclear cells (PBMC) of 12 patients were collected at baseline and during treatment. In parallel to the decline in viral load, we found a decline in circulating Treg, combined with an increase in HBV core antigen-specific IFN-gamma production and proliferation. The production of IL10 did not decrease during therapy. In conclusion, adefovir induced viral load reduction results in a decline of circulating Treg together with a partial recovery of the immune response.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Center Rotterdam, 's-Gravendijkwal 230, Room Ca 326, 3015 CE Rotterdam, The Netherlands. j.n.stoop@erasmusmc.nl
authors.forename: Jeroen N
authors.initials: JN
authors.lastname: Stoop
authors.forename: Renate G
authors.initials: RG
authors.lastname: van der Molen
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D063065:Organophosphonates; D016753:Interleukin-10; D007371:Interferon-gamma; D000225:Adenine; C106812:adefovir dipivoxil