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

摘要

Objective To study the effects of thymus transplantation(TT)combined with CD4--DLI on T cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT). 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 transplanta-tion 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 day 0,C57BL/6 mice were used as donor for hematopoietic stem cell transplantation. The mice were sacrificed on 5 days,2 weeks,4 weeks and 3 months 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 reconstitu-tion. 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 pro-duction 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.%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5d、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.