Haller G W, Esnaola N, Yamada K, Wu A, Shimizu A, Hansen A, Ferrara V R, Allison K S, Colvin R B, Sykes M, Sachs D H
Transplantation Biology Research Center, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston 02129, USA.
J Immunol. 1999 Oct 1;163(7):3785-92.
Thymic tissue transplantation has been performed previously in adult mice to induce donor-specific tolerance across allogeneic and xenogeneic barriers. We have now attempted to extend this technique to a large animal preclinical model and describe here our initial studies of allogeneic thymic transplantation in miniature swine. Two miniature swine were thymectomized before thymic tissue transplantation, and two remained euthymic. Donor thymic tissue was harvested from SLA class I-mismatched juvenile pigs and placed into recipient sternocephalicus muscle, kidney capsule, and omentum. A 12-day course of cyclosporin A was started on the day of transplantation. Allogeneic thymic engraftment could only be achieved in euthymic and not in thymectomized miniature swine using this treatment regimen. Both nonthymectomized animals showed good graft development, with evidence of thymopoiesis, as indicated by positive CD1 and host-type SLA class I immunoperoxidase staining of immature graft-infiltrating cells. Both animals also demonstrated donor-specific T cell hyporesponsiveness, as measured by MLR and cell-mediated lympholysis. The thymic grafts continued to develop despite the appearance of high levels of anti-donor specific cytotoxic IgG Abs. Thus, thymic tissue transplanted across an SLA class I barrier can engraft and support host thymopoiesis in euthymic miniature swine. The presence of the host thymus was required for engraftment. These data support the potential of thymic transplantation as part of a regimen to induce donor-specific tolerance to xenogeneic organ grafts.
胸腺组织移植此前已在成年小鼠中进行，以诱导跨越同种异体和异种屏障的供体特异性耐受。我们现在试图将这项技术扩展到大型动物临床前模型，并在此描述我们在小型猪中进行同种异体胸腺移植的初步研究。两只小型猪在胸腺组织移植前进行了胸腺切除，另外两只保留胸腺。供体胸腺组织取自SLA I类不匹配的幼年猪，并植入受体的胸骨头肌、肾包膜和大网膜。移植当天开始为期12天的环孢素A疗程。使用这种治疗方案，同种异体胸腺植入仅在有胸腺的小型猪中实现，而在胸腺切除的小型猪中未实现。两只未进行胸腺切除的动物均显示出良好的移植物发育，有胸腺生成的证据，未成熟移植物浸润细胞的CD1和宿主型SLA I类免疫过氧化物酶染色呈阳性。通过混合淋巴细胞反应（MLR）和细胞介导的淋巴细胞溶解测定，两只动物均表现出供体特异性T细胞低反应性。尽管出现了高水平的抗供体特异性细胞毒性IgG抗体，但胸腺移植物仍继续发育。因此，跨越SLA I类屏障移植的胸腺组织可以在有胸腺的小型猪中植入并支持宿主胸腺生成。植入需要宿主胸腺的存在。这些数据支持胸腺移植作为诱导对异种器官移植物供体特异性耐受方案一部分的潜力。
