树突状细胞特异表达TGF-β和自身抗原表位诱导免疫耐受

Induction of specific immune tolerance is the ideal method to prevent transplantation rejection and autoimmune diseases. It is confirmed that immature dendritic cells (iDCs) can induce immune tolerance and TGF-β1 can keep DCs in a immature state. Immune therapeutic target was autoantigen PLP130-151 in our project. An adenovirus vector was constructed carrying TGF-β1 and chimeric PLP130-151/immuglublin driven by class Ⅱ transactivator (CⅡTA) type I promoter which can express specifically in DCs. In Vitro, costimulatory molecules expression levels on the surface of DCs transducted with the adenovirus constructed lowed significantly and their ability to stimulate proliferation of allogeneic T cells was suppressed. Protective tests was done by adenovirus carrying two genes and the control adenovirus in EAE models .Amelioration of clinic symptom, suppression of lymphocyte response to PLP, decrease of Th1/Th2 ratio and number reduction of TCRVβ8.2 positive cells were observed, but autoantibody levels change was not significantly. Our study indicated that transduction DCs with adenovirus carrying TGF-β1 and autoantigen can Ameliorate clinic symptom and the protective effect was, to a large extent, due to the inhabitation of DCs maturation , and may be a potential candidate for use in preventing and treating patients with MS.

以自身抗原PLP139-151表位为免疫治疗靶点，构建携带TGF-B和PLP抗原表位/Ig嵌合基因的俨《驹靥澹瑿D11c启动子调控，在树突状细胞特异性表达。通过TGF-B诱导产生非成熟树蛔聪赴胱陨砜乖哟ィ够宥宰陨砜乖匾煨悦庖吣褪堋９鄄烀庖吣褪艹潭取⒊中奔浼岸允笛樾宰陨砻庖咝阅约顾柩椎谋；ぶ瘟谱饔茫教制浞乐巫陨砻庖卟〉目尚行浴