CD4 + CD25 + FoxP3 + T regulatory cells in subjects responsive or unresponsive to hepatitis B vaccination / 中南大学学报(医学版)

ABSTRACT

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 ).Conclusion 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-γhyposecretion in PBMCs.