Astragalus polysaccharides regulate T cell-mediated immunity via CD11chighCD45RBlow DCs in vitro

Ethnopharmacological relevanceAstragalus polysaccharides (APS) isolated from one of the Chinese herbs, Astragalus mongholicus, are known to have a variety of immunomodulatory activities. However, it is not yet clear whether APS can induce the activation and differentiation of dendritic cells (DCs) and subsequently activate T cells.Aim of the studyThis study was carried out to investigate the effect of APS on the differentiation of splenic DCs and its influence on T cell-mediated immunity through interleukin (IL)-12-producing CD11chighCD45RBlow DCs in vitro.MethodologyMACS microbeads were used to isolate splenic DCs, CD11chighCD45RBlow DCs, CD11clowCD45RBhigh DCs and CD4+ T cells. Phenotypes were analyzed by flow cytometry, and cytokine levels were determined with cytometric bead array or ELISA.ResultThe percentage of CD11chighCD45RBlow DCs was significantly increased after treatment with APS compared to their counterparts. The cytokine secretion pattern of CD11chighCD45RBlow DCs and CD11clowCD45RBhigh DCs was detected, and it was found that unlike the stable IL-10 secretion pattern of CD11clowCD45RBhigh DCs induced by APS, CD11chighCD45RBlow DCs showed a dose-dependent relationship between IL-12 production and APS stimulation. In order to verify whether the activation of CD4+ T was associated with the differentiation of splenic DCs mediated by APS to CD11chighCD45RBlow DCs, anti-IL-12 receptor (IL-12R) as well as anti-IL-10R monoclonal antibody was used to inhibit the effect of CD11chighCD45RBlow DCs and CD11clowCD45RBhigh DCs in CD4+ T mixed lymphocyte reaction culture. After treatment with anti-IL-12R or anti-IL-10 monoclonal antibody in CD4+ T+CD11chighCD45RBlow DCs or CD11clowCD45RBhigh DCs mixed lymphocyte reaction, the inductions of these DCs on T cells were inhibited dramatically.ConclusionAPS might induce the differentiation of splenic DCs to CD11chighCD45RBlow DCs followed by shifting of Th2 to Th1 with enhancement of T lymphocyte immune function in vitro. Also, the effect of APS on T-cell differentiation to Th1 was not associated with the inhibition of IL-10 production in CD11clowCD45RBhigh DCs.

Astragalus polysaccharides (APS) isolated from one of the Chinese herbs, Astragalus mongholicus, are known to have a variety of immunomodulatory activities. APS (50, 100, 200 μg/ml) stimulation could induce the differentiation of splenic DCs to IL-12-producing CD11chighCD45RBlow/CD11chigh DCs (R2), and further induce activation of immune function of T lymphocyte with shifting of Th2 to Th1 in vitro. In addition, the effect of APS on T-cell differentiation to Th1 was not associated with the inhibition of IL-10 production in CD11clowCD45RBhigh/CD45RBhigh DCs (R4).Figure optionsDownload as PowerPoint slide