Astragalus polysaccharides regulate T cell-mediated immunity via CD11c(high)CD45RB(low) DCs in vitro.
BACKGROUND
Astragalus 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.


OBJECTIVE
This 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 CD11c(high)CD45RB(low) DCs in vitro.


METHODS
MACS microbeads were used to isolate splenic DCs, CD11c(high)CD45RB(low) DCs, CD11c(low)CD45RB(high) DCs and CD4(+) T cells. Phenotypes were analyzed by flow cytometry, and cytokine levels were determined with cytometric bead array or ELISA.


RESULTS
The percentage of CD11c(high)CD45RB(low) DCs was significantly increased after treatment with APS compared to their counterparts. The cytokine secretion pattern of CD11c(high)CD45RB(low) DCs and CD11c(low)CD45RB(high) DCs was detected, and it was found that unlike the stable IL-10 secretion pattern of CD11c(low)CD45RB(high) DCs induced by APS, CD11c(high)CD45RB(low) 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 CD11c(high)CD45RB(low) DCs, anti-IL-12 receptor (IL-12R) as well as anti-IL-10R monoclonal antibody was used to inhibit the effect of CD11c(high)CD45RB(low) DCs and CD11c(low)CD45RB(high) DCs in CD4(+) T mixed lymphocyte reaction culture. After treatment with anti-IL-12R or anti-IL-10 monoclonal antibody in CD4(+) T+CD11c(high)CD45RB(low) DCs or CD11c(low)CD45RB(high) DCs mixed lymphocyte reaction, the inductions of these DCs on T cells were inhibited dramatically.


CONCLUSIONS
APS might induce the differentiation of splenic DCs to CD11c(high)CD45RB(low) 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 CD11c(low)CD45RB(high) DCs.
Liu
Qing-yang
QY
Department of Microbiology and Immunology, Burns Institute, First Hospital affiliated to the Chinese PLA General Hospital, 51 Fu-Cheng Road, Beijing, PR China. LLQQ2003YY@yahoo.com.cn
Yao
Yong-ming
YM
Zhang
Shu-wen
SW
Sheng
Zhi-yong
ZY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D027883:Astragalus Plant / Q000737:chemistry*; D018845:CD11 Antigens / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology*; D011134:Polysaccharides / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D015704:CD4 Antigens; D007155:Immunologic Factors; D010936:Plant Extracts; D011134:Polysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D017493:Leukocyte Common Antigens