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[摘要]
目的: 探讨吲哚胺2,3双加氧酶(indoleamine 2,3 dioxygenase,IDO)基因修饰的树突状细胞(dendritic cells,DCs)在体外对造血干细胞移植物中异基因T细胞增殖反应的抑制作用。方法: 用携带IDO基因的重组腺病毒转染BALB/c小鼠(受体)骨髓来源的DCs ,用RT PCR法检测DCs表面IDO的表达,用流式细胞术分析IDO基因修饰前后DC表型的变化,并把IDO DC与C57BL/6小鼠(供体)脾脏来源的T淋巴细胞共培养,通过混合淋巴细胞培养等方法检测异基因T细胞的特异性反应性和诱导T细胞凋亡的情况。结果: 用腺病毒载体携带的IDO基因转染DCs后,DCs可有效表达IDO,且没有影响DC的表型;IDO基因修饰的DCs可抑制异基因T细胞的增殖反应,同时可诱导异基因反应性T淋巴细胞的凋亡。结论: 在体外,IDO基因修饰的DCs可抑制移植物中异基因T淋巴细胞的增值反应。移植用该种方法处理过的骨髓,可能会预防移植物抗宿主病(GVHD)的发生。
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[Abstract]
Objective: To study the inhibitory effect of indoleamine 2,3-dioxygenase(IDC)-modified dendritic cells on proliferation responses of allogeneic T-cell in transplantation of the hematopoietic stem cells in vitro. Methods: BALB/c mice bone marrow-derived dendritic cells were transfected with recombinant adenovirus harboring AdIDO gene. IDO mRNA was detected by RT-PCR in DCs transfected with AdmIDO and the changes of DCs phenotype were analyzed by FACS. Naive T lymphocytes from the spleen of C57BL/6 mice were co-cultured with BALB/c mouse-derived IDO-DC and Mixed lymphocyte reaction were performed to evaluate the alloantigen-specific hyporesponsivness and T cell apoptosis.
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