Objective: To investigate the suppressive effect of CD4+CD25+ regulatory T cells from mice infected with Schistosoma japonicum.
Methods: BALB/c mice were infected with S. japonicum. At 6 and 13 weeks post-infection, the spleens were removed and CD4+CD25+ T cells were separated by magnetic beads. In in vitro experiments, CD4+CD25+ T Cells were cocultured with CD4+CD25- T cells. The inhibitory role of the CD4+CD25+ T cells was assessed by [3H] thymidine incorporation method and the cytokines in the cultural supernatant were detected by ELISA. In in vivo experiments, mice inoculated with irradiated cercariae of S. japonicum were adoptively transferred with CD4+CD25+ T cells isolated from the mice chronically infected with S. japonicum. The intracellular cytokine expressions of splenocytes were performed by flow cytometry, and sera IgG1 and IgG2a antibodies against irradiated cercaria antigens were detected by ELISA.
Results: In vitro, CD4+CD25+ T cells were able to suppress the proliferation of CD4+CD25- T cells when stimulated with SEA, compared with single CD4+CD25- T cells culture (cpm 7615 +/- 1 058) (P < 0.01). Furthermore, CD4+CD25+ T cells isolated from mice chronically infected with S. japonicum presented higher suppressive efficacy (cpm 2 336 +/- 490), compared with that isolated from the acutely infected mice (cmp 4 467 +/- 144) (P < 0.05). Meanwhile, CD4+CD25+ T cells isolated from mice with the acute infection inhibited the cytokine secretion by CD4+CD25- T cells and the suppression rate was 32.0% for IL-4 (P < 0.05), 66.3% for IFN-gamma (P < 0.01) and 63.2% for IL-2 (P < 0.01), respectively, and CD4+CD25+ T cells isolated from mice with the chronic infection, the suppression rate was 28.4% for IL-4 (P < 0.05), 60.1% for IFN-gamma (P < 0.01) and 58.3% for IL-2 (P < 0.01), respectively. In vivo, IFN-gamma secretion and IgG2a antibody production of mice adoptively transferred with CD4+CD25+ T cells from the chronically infected mice were suppressed when mice were inoculated with irradiated cercariae of S. japonicum (P < 0.05).
Conclusion: CD4+CD25+ T cells isolated from mice infected with S. japonicum have played roles of Th1-dominant immune suppression.