目的探讨抗γ公共链单克隆抗体(抗γc单抗)联合供者脾细胞特异性输注(DST)诱导移植物长期存活的可行性及相关机制。方法建立小鼠颈部异位心脏移植模型,组Ⅰ为单纯实施心脏移植组,组Ⅱ于移植前给予DST,组Ⅲ术前予DST联合抗托单克隆抗体处理,术后观察移植物的存活时间及相关指标。结果组Ⅲ心脏移植物平均存活时间明显长于组Ⅰ及组Ⅱ(P〈0.05)。FACS分析显示组Ⅲ受者脾细胞中Tr比例较组Ⅰ及组Ⅱ显著增高(P〈0.05),同时脾细胞增殖活性明显减低(P〈0.05)。结论抗γ公共链单克隆抗体联合DST通过增加供者体内Tr的比例,减低对同种抗原的应答能力,显著延长同种心脏移植模型中移植物存活时间。
Objective To investigate whether blocking Tc signals combined with donor specific tramafion (DST) can induce longterm engraftment or transplant tolerance and its mechanism. Methods The recipients (C57BL/6 mice) were randomly divided into 3 groups (each group includes 6 mice) and cervical heterotopic cardiac transplantafions were performed with the Balb/c mice as donors. In group Ⅰ (control group), the recipients underwent the transplantation without any pretre.atment; in group Ⅱ , the transplantations were performed 7 days after DST; in group Ⅲ, except pretreatment with anli-γc antibodies, the recipients received the same treatment as group Ⅱ . The mean survival time of the grafts, the regulatory T cell ratio, the allow.active T cell activation, and the generation ability were recorded and detected. Results The mean survival time of the cardiac grafts in groupⅢ was signitleandy prolonged comparing with that of group Ⅰ and groupH ( P 〈 0.05). In group Ⅲ, the activation and generation ability of alloreacfive T cells decreased ( P 〈 0.05) but the regulatory T cell ratio increased ( P 〈 0.05) as comparing with those in group Ⅰ and group Ⅱ . Conclusion Blockade of γc signaling in combination with DST can remarkably prolong cardiac allograft survival, which may be associated with inhibition of antigen-specific T cell proliferation and induction of alloreactive T clones deletion together with a state of specific engraftment of alloanligen or tolerance.