Immunomodulatory effect and its mechanism of triepoxide on regulatory dendritic cells
- Author:
Yi-wen ZHAO
1
Author Information
1. Department of Nephrology
- Publication Type:Journal Article
- Keywords:
Dendritic cells;
Immunity;
Regulatory;
T-lymphocytes;
Tripdiolide
- From:
Medical Journal of Chinese People's Liberation Army
2012;37(10):792-795
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the influence of triepoxide (TPT) on the function of CD11clowCD45RBhigh dendritic cell (DC) subsets which produce IL-10. Methods Splenic CD11clowCD45RBhigh DCs and CD4+ T cells were harvested from C57BL/6 mice by magnetic bead sorting. CD11clowCD45RBhigh DCs were treated with various doses of TPT (0, 1, 10, 20ng/ml), and those without TPT as controls. Flow cytometry was used to determine the expression of CD11clowCD45RBhigh DC surface molecules including CD40, CD80, CD86, I-a/e, and IL-10 levels in CD11clowCD45RBhigh DC culture supernatants were determined by sandwich enzyme-linked immunosorbent assays (ELISA). The CD4+ T cells were divided into the following 5 groups: control group, untreated group (TPT-untreated CD11clowCD45RBhigh DC+CD4+ T cells), high-dose TPT-treated group (20ng/ml TPT-treated CD11clowCD45RBhigh DC+CD4+ T cells), high-dose TPT-treated + antibody I group (20ng/ml TPT-treated CD11clowCD45RBhigh DC+CD4+ T cells and IL-10 antibody) and high-dose TPT-treated + antibody II group (20ng/ml TPT-treated CD11clowCD45RBhigh DC+CD4+ T cells and IL-10 antibody isotype). Proliferative activity of CD4+ T lymphocytes was determined by MTT, whereas IL-4 and IFN-γ contents in CD4+ T cell culture supernatants were determined by flow cytometry. Results TPT markedly decreased the expression of CD40 and I-a/e while enhancing the expression of CD86 on CD11clowCD45RBhigh DC surface and IL-10 secretion. The enhancement of IL-10 secretion level hinged upon the rise of TPT concentration. The proliferative activity and IFN-γ secretion level in high-dose TPT-treated group and high-dose TPT-treated + antibody II group were markedly lower than those in the untreated group with significantly higher IL-4 secretion levels in TPT, whereas the proliferative activity and IFN-γ secretion level in high-dose TPT-treated group and high-dose TPT-treated + antibody I group were significantly higher than those in the untreated group with markedly lower IL-4 secretion level in TPT. Conclusions TPT could activate the secretion of IL-10 by CD11clowCD45RBhigh DCs, and further induce activation of immune function of T lymphocyte with shifting of Th1 to Th2 in vitro. TPT may down-regulate the immune response by promoting the phenotypic and functional maturation of CD11clowCD45RBhigh DC.
