title: CD4(+) CD25(+)  FoxP3(+)  T regulatory cells in subjects  responsive or unresponsive to hepatitis B vaccination.
abstract: OBJECTIVE
  To determine CD4(+) CD25(+) T regulatory cells (Tregs), forkhead box P3 (FoxP3) mRNA expression and levels of cytokines secreted by peripheral blood mononuclear cells (PBMCs) in individuals responsive or unresponsive to hepatitis B (HB) vaccination, and to explore the relationships between immune response and immune regulatory cells or cytokines.
  
  
  METHODS
  Based on the antibody against hepatitis B surface antigen (HBsAg) after HB vaccination, the CD4(+) CD25(+) Tregs frequencies in PBMCs from 18 responders, 22 nonresponders and 10 non-immunized healthy controls were analyzed by flow cytometry. The expression of FoxP3 mRNA in PBMCs with or without stimulation of phytohemagglutinin (PHA)and HBsAg was analyzed by real-time quantitative PCR. Levels of IL-4, IL-12, IL-18, and IFN-γ secreted by PBMCs after PHA and HBsAg stimulation were analyzed by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The ratio of CD4(+) CD25(+) Tregs to CD4(+) T cells in the nonresponders was markedly higher than that in the responders (P<0.05), but lower than that in the controls (P<0.01). FoxP3 was differentially expressed among the responders, nonresponders, and controls in PBMCs before and after PHA and HBsAg stimulation, and nonresponders had the highest FoxP3 mRNA expression (P<0.05 or P<0.01). The content of IFN-γ by PBMCs after PHA and HBsAg stimulation was markedly lower in the nonresponders as compared with the controls and responders (P<0.05). However, there were no significant differences in the levels of IL-18, IL-4, and IL-12 from PBMCs after PHA and HBsAg stimulation between the responders and controls as well as the nonresponders (P>0.05).
  
  
  CONCLUSIONS
  CD4(+) CD25(+) FoxP3(+) Tregs may be involved in the negative regulation of responses to hepatitis B vaccination. Immunologic non-responses to hepatitis B vaccination may be related to IFN-γ hyposecretion in PBMCs.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Li
authors.forename: Deming
authors.initials: D
authors.lastname: Tan
authors.forename: Hongbo
authors.initials: H
authors.lastname: Liu
authors.forename: Kecheng
authors.initials: K
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000917:Antibody Formation; D016022:Case-Control Studies; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D017325:Hepatitis B Vaccines; D007378:Interleukins; D012333:RNA, Messenger; D007371:Interferon-gamma