FasL基因转染树突状细胞在抑制实验性自身免疫性葡萄膜炎中的作用

目的:探讨FasL基因转染的抗原特异性树突状细胞(DC)对实验性自身免疫性葡萄膜炎(EAU)的抑制作用.方法:用携带FasL基因的腺病毒转染DC和负载自体抗原——光感受器间维生素A类结合蛋白(IRBP)R16肽段的DC,制备FasL转染的DC(FasL-DC)和抗原负载FasL-DC(“杀伤性”DC).检测FasL基因...

Suppressive effect of FasL-transfected dendritic cells on experimental autoimmune uveoretinitis

Objective： To investigate the inhibitory effects of antigewspecific FasL-transfected dendritic cells （DCs） on the development of experimental autoimmune uveoretinitis （EAU）. Methods： FasL-transfected DC （FasL-DC） and antigen-loaded FasL-DCs （＂killer DCs＂） were generated from mouse mature DC （mDC） using adenoviral gene transfer. The expression of FasL gene, survival, the mature phenotype of FasL-DC and T cell proliferation induced by FasL-DC were analyzed. EAU in C57BL/6 mice was induced by immunization with human interphotoreceptor retinoid-binding protein （hIRBP） R16 peptide. The effect of proliferation and apoptosis of primary T cells and activated primary T cells in cocultures with antigen-loaded FasL-DC,and the proliferation of activated primary T cells induced antigen-loaded FasL-DC in the presence of a blocking anti-FasL antibody were investigated in vitro. Results： Transduction of DCs resulted in FasL over expression without affecting the survival, mat uration of phenotype, and T cell proliferation. The proliferation of primary T cells and activated primary T cells was inhibited in cocultures with antigen-loaded FasL-DC due to induction of apoptosis. The reduction in activated primary T cell proliferation could be blocked by an anti-FasL antibody. Conclusions： The results demonstrate that antigen-loaded FasL-DC eliminates autoreactive T cells in an antigen-specific manner, and manipulation of ＂killer DCs＂ might be considered to be a potential therapy for human uveitis with an autoimmune origin.