学术
吲哚胺2，3-二氧化酶基因修饰的DCs对小鼠移植物抗宿主病的抑制作用
史平[1] 楼国良[1] 周俊平[1] 张文颖[1] 朱海沫[1] 王梁华[2] 焦炳华[2]
[1]第二军医大学附属长海医院特需诊疗科,上海200433 [2]第二军医大学基础医学部生化与分子生物教研室,上海200433
摘 要:
目的：探讨小鼠树突状细胞（dendritic cells，DCs）转染吲哚胺2，3-二氧化酶（indolamine2，3-dioxygenase，IDO）基因后对移植物抗宿主病（graft versus host disease，GVHD）的抑制作用。方法：用携带IDO基因的重组腺病毒感染BALB／c小鼠来源的树突状细胞，后者与C57BL／6小鼠骨髓移植物共培养，将经过处理的骨髓移植给BALB／c小鼠（C57BL／6→BALB／c小鼠GVHD模型，H-2^b→H-2^d），观察、比较各组GVHD表现（包括GVHD评分、生存期、病理学改变），并行嵌合体检测及观察混合淋巴细胞反应（mixed lymphocyte reaction，MLR）。结果：致死剂量照射的受体小鼠接受经IDO处理的骨髓移植（bone marrow transplantation，BMT）后，未出现明显的GVHD反应，生存期显著延长，3个月时生存率大于80％；对照组均在移植后2周左右出现明显的GVHD表现，生存期未超过1个月。IDO—DC治疗组未出现明显的组织病理学损害；3个月时IDO-DC治疗组仍然保持比较高的嵌合；IDO-DC组的T细胞对C57BL／6、BALB／c淋巴细胞的反应性与对C3H淋巴细胞反应性相比显著降低（P〈0．05）。结论：经IDO基因修饰的DCs可以选择性去除骨髓移植物中异基因反应性T细胞，从而特异性地抑制GVHD并能及早地免疫重建。[著者文摘]
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文章出处:
《中国肿瘤生物治疗杂志》-2007年14卷5期 -423-427页
栏目信息:
分 类 号:
文献标识码:
A
文章编号:
1007-385X（2007）05-0423-05
Inhibition of graft-versus-host disease by indolamine 2,3-dioxygenase gene-modi- fled dendritic cells
SHI Ping , LOU Guo-liang , ZHOU Jun-ping , ZHANG Wen-ying , ZHU Hai-mo , WANG Liang-hua, JIAO Bing- hua （ 1. Department of Special Clinic, Changhai Hospital, Second Military Medical University, Shanghai 200433, China ; 2. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Second Military Medical Uni- versity, Shanghai 200433, China）
Abstract:
Objective： To study the inhibitory effect of dendritic cells modified by indolamine 2, 3-dioxygenase （IDO） against graft-versus-host disease （GVHD）. Methods： BALB/c-derived dendritic cells （DCs） were transfected with recombinant adenovirus harboring IDO gene and the product was co-cultured with bone marrow graft of C57BL/6 mice. Mod- ified bone marrow graft was transplanted into BALB/c mice （C57BL/6 to BALB/c mice GVHD model system, H^-2b→H- 2^d）. The symptoms of GVHD （GVHD score, survival period, pathological changes） were observed and compared between different groups. Detection of engraftment and mixed lymphocyte reaction were also performed. Results： Mice treated with lethal dose irradiation had no obvious GVHD symptoms after transplanted with IDO-modified bone marrow, and had prolonged survival period, with the 3-month survival rate higher than 80%. Mice in the control group had obvious GVHD symptoms 2 weeks after transplantation, with a survival period less than 1 month. IDO-DC treatment group had no obvious pathological lesions and showed higher engraftment after 3 months. T cells in IDO-DC group had a lower reactivity to C57BL/6, BALB/c lymphocytes than to C3 H lymphocytes （P 〈 0. 05 ）. Conclusion： IDO gene-modified DCs can specifically deplete alloreactive T cells from bone marrow graft.[著者文摘]
Key words:
indolamine 2,3-dixygenase; dendritic cells; malignant hematopathy; allogineic hematopoietic stem cell transplantation; graft versus host disease
基金资助:
全军医学科研十一五计划面上项目（N0.01MA159）.
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