人FasL基因转染成熟树突状细胞对T淋巴细胞增殖和凋亡的影响

Dendritic Cells Genetically Engineered to Express Fas Ligand Regulate T Lymphocyte Proliferation and Apoptosis

探讨转染人FasL基因的成熟树突状细胞(DC)对异体T淋巴细胞增殖和凋亡的影响,为实现临床器官移植免疫耐受提供初步实验依据.从健康成年人外周静脉血中获得成熟树突状细胞.将人FasL基因成功转染成熟树突状细胞,检测其表面分子的表达和自身凋亡情况,并对其抗原递呈功能进行分析.从异体健康成人外周血中获取T淋巴细胞,将转染成功的树突状细胞与T淋巴细胞混合培养,检测其对T淋巴细胞增殖和凋亡的影响.结果表明:人FasL基因转染没有明显影响成熟树突状细胞表面分子CD40、CD80、CD86和HLA-DR的表达;没有诱导树突状细胞自身发生凋亡;没有影响DC的抗原递呈功能.转染FasL基因后的树突状细胞使异体T淋巴细胞刺激指数明显下降,凋亡增加.因此认为,人FasL基因转染对成熟树突状细胞的表面分子表达、自身凋亡、抗原递呈等生物学性状无影响;转染FasL基因的树突状细胞使异体T淋巴细胞的增殖能力减弱,并能明显诱导T淋巴细胞凋亡.

To investigate the effects of dendritic cells on T lymphocyte proliferation and apoptosis,providing an in vitro model of clinical transplant immunological tolerance.After mature dendritic cells（mDCs） from peripheral blood of healthy adults was successfully transfected with human FasL gene,mDCs were analyzed for the expression of cell surface molecules,antigen presenting function and their apoptosis.Effects of mDCs on T lymphocyte proliferation and apoptosis were further detected based on co-culture of mDCs and T lymphocytes.The results show that,FasL did not significantly change the expression level of mDC’s surface molecules CD40,CD80,CD86 and HLA-DR;FasL did not induce apoptosis of mDC.No effects on the antigen presenting function of mDC were observed as well.The mDC transfected with FasL decreased stimulation index and increased apoptosis of allogeneic T-lymphocyte significantly.So that,human mDCs transfected with FasL may regulate T lymphocyte proliferation and apoptosis without alteration of cell surface molecules and antigen presentation characteristics on human mDC.