吲哚胺2,3双加氧酶基因修饰的DCs对同种异基因T细胞增殖反应的抑制

Inhibition of allogeneic T-cell proliferation by indoleamine 2,3-dioxygenase-modified dendritic cells

目的探讨吲哚胺2,3双加氧酶(indoleamine2,3dioxygenase,IDO)基因修饰的树突状细胞(dendriticcells,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。

Objective： To study the inhibitory effect of indoleamine 2,3-dioxygenase （IDC）-modified dendritic cells on proliferation responses of allogeneie T-cell in transplantation of the hematopoietie stem cells in vitro. Methods： BALB/c mice bone marrow-derived dendritic cells were transfeeted with recombinant adenovirus harboring AdlDO gene. IDO mRNA was detected by RT-PCR in DCs transfected with AdmlDO and the changes of DCs phenotype were analyzed by FACS. Naive T lymphoeytes 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-speeifie hyporesponsivness and T cell apoptosis. Results： DCs effectively expressed IDO after transfeetion, without influencing the phenotype of DCs. IDO-transfeeted DCs were found to inhibit alloreactive T cells proliferation and induce T cell apoptosis. Conclusion： DCs transfeeted with IDO gene may prevent graft-versus-host disease through inhibiting alloreaetive T cells proliferation in haematopoietie stem cell grafts.