Effects of short-course immunosuppression on chimerism and tolerance induced by BMT without cytoreductive conditioning
- Author:
- No author available
- Journal Title:
- CHINESE JOURNAL OF ORGAN TRANSPLANTATION
- Issue:
- 11
- DOI:
- 10.3760/cma.j.issn.0254-1785.2006.11.004
- Key Word:
- 免疫耐受;移植嵌合体;环孢菌素;皮肤移植
Abstract： 目的 探讨临床常用免疫抑制剂对供者骨髓移植和T淋巴细胞协同刺激信号阻滞联合诱导的混合嵌合体和免疫耐受的影响.方法 将BALB/c小鼠的皮肤移植于C57BL/6小鼠背部,术后经尾静脉注射BALB/c小鼠骨髓细胞5×107个和AdCTLA4-FasL 5×109PFU(标准方案组),部分小鼠在此基础上还接受环孢素A(CsA组)、霉酚酸酯(MMF组)和环孢素A、霉酚酸酯联合(CsA+MMF组)皮下或腹腔注射,共用药28 d,同时设移植后不给任何处理的对照组.观察移植皮肤存活情况,流式细胞仪测定受者外周血Vβ11+T淋巴细胞的水平和供者来源细胞的嵌合水平,行单向混合淋巴细胞反应(MLR)了解受者对供者抗原的反应.结果 除对照组外,其它几个组在短期内(21d)均诱导了高水平的混合嵌合体(＞30%),但在停药后的140 d,仅标准方案组和MMF组仍保持稳定的嵌合水平.对照组移植皮片的存活时间为(9.8±1.2)d,CsA组和CsA+MMF组皮片存活时间均不超过50 d,标准方案组和MMF组皮片存活时间均超过150 d,明显长于CsA组和CsA+MMF组(P＜0.05).术后150d,标准方案组和MMF组的MLR受到显著抑制,刺激指数均＜1,而CsA组和CsA+MMF组的MLR未受抑制(刺激指数均＞1).术后21d时,各组小鼠外周血中Vβ11+T淋巴细胞的水平均低于对照组,但标准方案组和MMF组的Vβ11+T淋巴细胞较CsA组和CsA+MMF组更低(P＜0.05),至术后140 d时,标准方案组和MMF组的Vβ11+T淋巴细胞比例降至更低水平.结论 CsA或含CsA的免疫抑制方案对供者骨髓移植和输注CTLA4-FasL联合诱导的混合嵌合体和免疫耐受具有抑制作用,其机理可能与早期外周供者反应性T淋巴细胞删除减少有关.
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