目的 探讨干预慢性迟发性超敏反应(DTH)与CD8^+T淋巴细胞的细胞毒等效应机制对同种小鼠心脏移植后慢性排斥反应的影响。方法 建立小鼠颈部异位心脏移植模型,实验组以BALB/c小鼠为供者,C57BL/6小鼠为受者,术后0、2、6及14d腹腔注射抗CD8单克隆抗体(抗CD8单抗)200μg/d,术后0、2及4d腹腔注射抗CD40L单克隆抗体(抗CD40L单抗)250μg/d;同系移植对照组供、受者均为BALB/C小鼠,术后同期腹腔注射等量生理盐水;同种移植对照组以BALWc小鼠为供者,C57BL/6小鼠为受者,术后不使用上述单抗。观察各组移植心的存活时间及移植心组织病理学变化。结果同种移植对照组移植心的平均存活时间为7.3d;实验组与同系移植对照组移植心的存活时间均超过60d。同种移植对照组移植心呈典型急性排斥反应病理学改变;同系移植对照组移植心组织未见明显病理变化;实验组移植心呈现血管周围炎、间质纤维化和血管内膜增生等慢性排斥反应组织病理改变。结论 清除CD8^+T淋巴细胞和阻断CD40/CD40L通路的处理方案虽可预防急性排斥反应,显著延长移植心的存活时间,但并不能阻止慢性排斥反应的发生。
Objective To evaluate the effect of delayed type hypersensitivity (DTH) and CD8 T lymphocyte cytotoxicity intervention on the development of chronic rejection in mouse cardiac allografts. Methods C57BL/6 (H-2^b) recipients either received a fully MHC-mismatched BALB/c (H-2^d)donor cardiac allograft or a C57BL/6 isograft. Allograft group was either treated with anti-CD154 (250 g intraperitoneally infusion on the day 0, 2 and 4) and a depleting CD8 mAb (200 μg intraperitoneally on the day 0, 2, 6 and 14) or with saline as control. The isograft group received saline infusion. The cardiac grafts were harvested for histological analysis while having long-term survival (〉60 days) or cessation of heart beating. Results Combined treatment with anti-CD154 mAb and anti-CD8 mAb resulted in significant prolongation of cardiac allografts survival but ultimately did not prevent the progression of chronic rejection, which showed transplant arteriosclerosis and interstitial fibrosis. Cardiac grafts lost due to serve acute rejection with mean survival time of 7. 3 days in allograft control group. No evidence of reiection appeared in isograft group. Conclusions Although short-term CD154 blockade in combination with CD8 T cell depletion could lower the incidence of acute rejection, thereby prolonging the survival of cardiac allografts significantly, it was insufficient to inhibit the development of chronic rejection.