LaMattina John C, Kumagai Naoki, Barth Rolf N, Yamamoto Shin, Kitamura Hiroshi, Moran Shannon G, Mezrich Joshua D, Sachs David H, Yamada Kazuhiko
Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
Transplantation. 2002 Mar 15;73(5):826-31. doi: 10.1097/00007890-200203150-00032.
Vascularized thymokidney transplants have previously been shown to induce tolerance across major histocompatibility complex barriers. The ability to perform vascularized thymic lobe transplantation could permit such tolerance to be induced with any cotransplanted solid organ or tissue. For this reason, we have developed a technique for vascularized thymic lobe transplantation in miniature swine.
Thymic vessels (n=2) were anastomosed to the carotid artery and the external jugular vein of naïve minor-mismatched recipients treated with a 12-day course of cyclosporine A (10 mg/kg/day). Graft survival and thymopoiesis were assessed by histology, immunohistochemistry, and fluorescence-activated cell sorting. Allele-specific antibodies 74-12-4 and pig allelic antigen (PAA) were used to distinguish donor and recipient cells.
Allografts showed intact cortical and medullary structure posttransplantation, without evidence of rejection or ischemia. Recipient thymocytes repopulated the donor cortical thymus by POD30 and increased in the cortex and medulla by POD60.
Our study demonstrates the technical feasibility of vascularized thymic lobe transplantation and the support of thymopoiesis by such transplants in a large animal model. This technique may offer a novel strategy to induce transplant tolerance across allogeneic and xenogeneic barriers, and to support long-term thymopoiesis in immunodeficient hosts.
先前已证明血管化胸腺肾移植可诱导跨越主要组织相容性复合体屏障的免疫耐受。进行血管化胸腺叶移植的能力可使任何共移植的实体器官或组织诱导出这种免疫耐受。因此，我们开发了一种在小型猪中进行血管化胸腺叶移植的技术。
将胸腺血管（n = 2）吻合至接受12天环孢素A（10 mg/kg/天）治疗的初次轻度错配受体的颈动脉和颈外静脉。通过组织学、免疫组织化学和荧光激活细胞分选评估移植物存活和胸腺生成。使用等位基因特异性抗体74-12-4和猪等位抗原（PAA）区分供体和受体细胞。
同种异体移植物移植后显示皮质和髓质结构完整，无排斥或缺血迹象。受体胸腺细胞在移植后第30天重新填充供体皮质胸腺，并在移植后第60天在皮质和髓质中增加。
我们的研究证明了血管化胸腺叶移植的技术可行性以及这种移植在大型动物模型中对胸腺生成的支持。该技术可能提供一种新策略，以诱导跨越同种异体和异种屏障的移植耐受，并支持免疫缺陷宿主中的长期胸腺生成。
