The Mechanism Of Immune Tolerance Caused By Echinococcusgranulosus Recombinant Antigen Of Eg10 And MMDH

ObjectiveTo identify the mechanism of mouse immune tolerance caused by Echinococcus granulosus recombinant Eg10 and m MDH. Methods1.We investigated the response of monocyte derived murine dendritic cells(DCs) to both recombinant antigens Eg10 and m MDH of Echinococcus granulosus. The morphology and the expression of IDO of DCs were examined using electron microscopy and immunocytochemistry.2.Before exposed to r Eg10 and rm MDH, DCs were treated with IDO inhibitor(1-MT). We evaluated the immunomodulatory potential of these antigens by several methods,e.g.the abilities of DCs to activate CD4+T cell proliferation and induce CD4+CD25+FOXP3+ Tregs were performed by MLR; the expression of cytokines were detected by Q-PCR;the surface molecules of DCs were analyzed by flow cytometry(FCM). Results1.Both recombinant Eg10 and m MDH failed to cause DCs maturation.2.DCs sitimulated by recombinant Eg10 and m MDH enhance the expression of IDO and the level of Kyn in DCs culture supernate. However,those responses will be inhibited by 1-MT.3.Compared with 1-MT untreated m MDH group,m MDH group treated with 1-MT performed a potent ability of activating CD4+T cell proliferation and a weaken ability of inducing CD4+CD25+FOXP3+ Treg. In contrast,1-MT can’t influence DCs of Eg10 group.4.DCs sitimulated by recombinant Eg10 and m MDH improved the levels of TNF-α、IL-6、IL-10 m RNA in different degrees,while the groups treated with 1-MT increased the level of TNF-α m RNA and decreased the levels of IL-6、IL-10 m RNA.5.DCs sitimulated by recombinant Eg10 and m MDH induce low expression of surface markers,and the groups treated with 1-MT failed to reverse the expression of surface markers. Conclusion1.Recombinant Eg10 and m MDH stimulated in vivo monocyte derived murine DCs,failed to cause DCs maturation and to stimulate CD4+T cell proliferation.2.DCs stimulated by recombinant m MDH induced high level of IDO and immune tolerance.3.There may be other mechanism of DCs immune tolerance by recombinant Eg10,rather than IDO-dependent tolerance mechanism.