Mohiuddin M, Kline G, Shen Z, Ruggiero V, Rostami S, DiSesa V J
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia.
J Thorac Cardiovasc Surg. 1993 Oct;106(4):632-5.
Permanent tolerance to an experimental cardiac allograft can be achieved by pretransplantation intrathymic inoculation of donor-specific lymphoid cells. We studied the effects of intrathymic inoculation of xenogeneic cells and intravenous cobra venom factor in a rodent model of cardiac xenotransplantation. Lewis rats underwent intraabdominal heterotopic heart transplantation with Syrian hamster donors. In untreated animals, mean graft survival time was 3 days. Five rats had 1 ml of antilymphocyte serum administered intraperitoneally. One day later, 2.5 x 10(7) hamster spleen cells were inoculated into the thymus under direct vision. Twenty-one days after antilymphocyte serum was given, heterotopic heart transplantation with a hamster donor was carried out. In all cases, rejection was accelerated and occurred between 20 minutes and 1 day after transplantation. Mean graft survival time was 5.2 hours (p < 0.0001 versus control). Six animals treated with antilymphocyte serum and intrathymic xenogeneic cells had 0.5 ml of cobra venom factor, a complement antagonist, administered intravenously 3 hours before transplantation and every other day thereafter. Mean graft survival was 3 days, which was not different from the response of naive animals. Animals treated with antilymphocyte serum only had no prolongation of graft survival (mean survival time 3 days, p = not significant). Animals treated with cobra venom factor alone (n = 5) before transplantation and on alternate days subsequently had mild graft prolongation with a mean survival time of 4 days (p = 0.0133). In contrast to experimental allograft models, intrathymic inoculation of xenogeneic cells produces hyperacute rejection in these naturally concordant species. The administration of cobra venom factor abrogates the hyperacute response, but the combination of cobra venom factor and intrathymic inoculation does not produce long-term graft survival.
通过移植前胸腺内接种供体特异性淋巴细胞，可实现对实验性心脏同种异体移植的永久耐受。我们在心脏异种移植的啮齿动物模型中研究了胸腺内接种异种细胞和静脉注射眼镜蛇毒因子的效果。将叙利亚仓鼠的心脏移植到Lewis大鼠的腹腔内，进行异位心脏移植。未经治疗的动物，平均移植物存活时间为3天。5只大鼠腹腔内注射1ml抗淋巴细胞血清。一天后，在直视下将2.5×10⁷个仓鼠脾细胞接种到胸腺内。给予抗淋巴细胞血清21天后，进行仓鼠供体的异位心脏移植。在所有情况下，排斥反应均加速，发生在移植后20分钟至1天之间。平均移植物存活时间为5.2小时（与对照组相比，p<0.0001）。6只接受抗淋巴细胞血清和胸腺内异种细胞治疗的动物在移植前3小时静脉注射0.5ml眼镜蛇毒因子（一种补体拮抗剂），此后每隔一天注射一次。平均移植物存活时间为3天，与未处理动物的反应无差异。仅接受抗淋巴细胞血清治疗的动物移植物存活时间未延长（平均存活时间3天，p无统计学意义）。移植前及随后隔天单独接受眼镜蛇毒因子治疗的动物（n = 5）移植物存活时间略有延长，平均存活时间为4天（p = 0.0133）。与实验性同种异体移植模型不同，在这些自然协同的物种中，胸腺内接种异种细胞会产生超急性排斥反应。给予眼镜蛇毒因子可消除超急性反应，但眼镜蛇毒因子与胸腺内接种联合使用并不能产生长期移植物存活。
