Cober S R, Randolph M A, Lee W P
Division of Plastic Surgery, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.
J Surg Res. 1999 Aug;85(2):204-8. doi: 10.1006/jsre.1999.5688.
Success has been reported using intrathymic injection in the preconditioning regimen to induce allograft tolerance. Although long-term stable tolerance has been achieved in numerous rodent vascularized solid organ allograft models, tolerance to skin transplants has only been achieved across minor antigenic or concordant species disparities. This study sought to induce tolerance across an allogeneic barrier in a rat model with a major genetic disparity.
Lewis rats were injected intrathymically with 1 x 10(8) Brown-Norway (BN) bone marrow cells and intraperitoneally with 1.0 cc of rabbit anti-rat anti-lymphocyte serum (ALS). Twenty-one days later, BN skin grafts were placed on the injected animals. Control groups were included to isolate the effect of technique, thymic manipulation, strain specificity, and ALS.
Animals receiving both intrathymic bone marrow cells and ALS had a skin graft median survival time of 24 days versus 8 days for the control group (P = 0.003). Groups receiving anti-lymphocyte serum alone or intrathymic bone marrow cell injection alone exhibited no skin graft survival prolongation. Mixed lymphocyte reactions revealed normal responsiveness of tolerant animal lymphocytes to donor strain lymphocytes.
This protocol utilizing the intrathymic injection of donor bone marrow cells along with short-term immunosuppression with anti-lymphocyte serum produced markedly prolonged survival of skin allografts transplanted across a major histocompatibility barrier. Although tolerance was incomplete, significant prolongation has not previously been reported in genetic disparities of this degree. These results suggest that the application of this technique for central immune modulation may be beneficial for allograft tolerance induction and deserves further study in large animals models.
已有报道称，在预处理方案中使用胸腺内注射可诱导同种异体移植耐受。尽管在众多啮齿动物血管化实体器官同种异体移植模型中已实现长期稳定耐受，但仅在次要抗原或协同物种差异的情况下才实现了对皮肤移植的耐受。本研究旨在在具有主要遗传差异的大鼠模型中诱导跨同种异体屏障的耐受。
将1×10⁸ 只棕色挪威（BN）骨髓细胞胸腺内注射给Lewis大鼠，并腹腔内注射1.0 cc兔抗大鼠抗淋巴细胞血清（ALS）。21天后，将BN皮肤移植物移植到注射过的动物身上。设置对照组以分离技术、胸腺操作、品系特异性和ALS的影响。
接受胸腺内骨髓细胞和ALS注射的动物，皮肤移植物的中位存活时间为24天，而对照组为8天（P = 0.003）。单独接受抗淋巴细胞血清或单独接受胸腺内骨髓细胞注射的组，皮肤移植物存活时间未延长。混合淋巴细胞反应显示，耐受动物淋巴细胞对供体品系淋巴细胞具有正常反应性。
该方案利用胸腺内注射供体骨髓细胞并结合抗淋巴细胞血清进行短期免疫抑制，显著延长了跨主要组织相容性屏障移植的皮肤同种异体移植物的存活时间。尽管耐受不完全，但此前尚未报道过这种程度的遗传差异有如此显著的延长。这些结果表明，这种用于中枢免疫调节的技术应用可能有利于诱导同种异体移植耐受，值得在大型动物模型中进一步研究。
