胸腺移植合并CD4^--DLI对异基因造血干细胞移植后T细胞重建的影响  

Effects of thymus transplantation combined with CD4^--DLI on T cell reconstitution after allogeneic hematopoietic stem cell transplantation

作　　者：秦建环 陈欣林 郑嘉坤 叶健滨 郑少玲 林贤雪 何满满 张玉明[2] 石明 QIN Jianhuan;CHEN Xinlin;ZHENG Jiakun;YE Jianbin;ZHENG Shaoling;LIN Xianxue;HE Manman;ZHANG Yuming;SHI Ming(Dongguan Key Laboratory of Environmental Medicine,Guangdong Medical University,523808 Dongguan,China)

机构地区：[1]广东医科大学东莞市环境医学重点实验室,广东省东莞市523808 [2]南方医科大学南方医院小儿科,广州市510515

出　　处：《实用医学杂志》2017年第14期2281-2287,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:81270632);广东省"扬帆计划"紧缺拔尖人才项目(编号:201433004);留学人员科技活动项目择优资助项目(编号:2QT14002);广东省普通高校特色创新项目(编号:2015KTSCX051)

摘　　要：目的研究胸腺移植(TT)合并CD4^--DLI对异基因造血干细胞移植(allo-HSCT)后T细胞重建的影响。方法将BALB/c小鼠随机分成3组,单纯造血干细胞移植(HSCT组),造血干细胞移植+胸腺移植(TT组),造血干细胞移植^+胸腺移植+去CD4^+T细胞的供体淋巴细胞输注(CD4^--DLI组)。移植前1 d,对小鼠进行致死剂量的放疗处理。移植当天,进行造血干细胞移植,供体为C57BL/6小鼠。移植处理后5 d、2周、4周、3个月分别处死小鼠,取小鼠外周血和脾脏细胞进行流式细胞术检测T细胞表面抗原,T细胞受体,初始T细胞,细胞内因子;HE染色观察供体胸腺的发育情况。结果 TT和CD4^--DLI不会影响彼此对T细胞重建的作用;TT合并CD4^--DLI能够通过胸腺依赖和胸腺非依赖两种途径加快CD4^+和CD8^+T细胞数目的重建、扩大初始CD4^+和CD8^+T细胞库、加快T细胞功能的重建,并且对TCR库和胸腺没有副作用。结论:TT合并CD4^--DLI可以加快allo-HSCT后T细胞重建。Objective To study the effects of thymus transplantation(TT)combined with CD4-DLI on T cell reconstitution after allogeneic hematopoietic stem cell transplantation(alloHSCT).Methods BALB/c mice were randomly divided into three groups:hematopoietic stem cell transplantation(HSCT group),hematopoietic stem cell transplantation combined with thymus transplantation(TT group)and hematopoietic stem cell transplantation combined with thymus transplantation plus CD4+T cell?depleted lymphocyte infusion(CD4-?DLI group).On day?1,the mice were treated with the lethal dose of radiotherapy.On day0,C57BL/6mice were used as donor for hematopoietic stem cell transplantation.The mice were sacrificed on5days,2weeks,4weeks and3months after transplantation,respectively.The peripheral blood and spleen cells of mice were collected for determinations of T cell surface antigen,T cell receptor,naive T cells and intracellular cytokines.HE staining was used to assess the development of donor thymus.Results TT and CD4-?DLI did not impair each other′s effects on T cell reconstitution.TT combined with CD4-?DLI increased the number of T cell reconstruction.CD4-?DLI promoted the effect of TT on enlargement naive CD4+and CD8+T cell pool.Combination of TT and CD4-?DLI enhanced the cytokine production of T cells.Conclusion TT combined with CD4-?DLI had no side effects on TCR repertoire and thymus.Conclusion TT combined with CD4-?DLI can enhance the reconstitution of T cell number and function via thymus dependent and thymus independent mechanism.

关 键 词：异基因造血干细胞移植 胸腺移植 淋巴细胞输注 T细胞重建 

分 类 号：R457.7[医药卫生—治疗学]