Occurrence of autoimmunity after xenothymus transplantation in T-cell-deficient mice depends on the thymus transplant technique
Occurrence of autoimmunity after xenothymus transplantation in T-cell-deficient mice depends on the thymus transplant technique
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DOI：
10.1097/tp.0b013e3181613f0c
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发表时间：
2008-02-27
期刊：
影响因子：
6.2
通讯作者：
Billiau, An D.
中科院分区：
文献类型：
--
作者：
Devos, Timothy;Sprangers, Ben;Billiau, An D.
胸腺鼠肾包膜下异胸腺移植常引起多器官自身免疫。在此，我们探讨这是否是异种胸腺移植的内在风险，还是取决于移植技术。我们开发了一种新的“静脉袋”胸腺移植技术（心脏-异种胸腺），并在大鼠-裸鼠模型中与传统的肾包膜下技术（肾-异种胸腺）进行了比较。尽管90%的肾异种胸腺移植小鼠产生了致死性自身免疫，但所有移植心脏异种胸腺的小鼠仍然完全健康。尽管t细胞生成明显改善，但心脏异种瘤受体的自身免疫缺失，并且与肾异种瘤受体相比，其CD4(+)CD25(+) t细胞频率和CD4(+)CD25（+）细胞Foxp3 mRNA水平显著升高。总之，我们描述了一种新的异种胸腺移植血管袋技术，可以阻止裸鼠自身免疫的发展。我们的数据进一步表明，自身免疫的预防与调节性t细胞的优越发育有关。
Xenothymus transplantation under the kidney capsule in athymic rodents frequently leads to multiorgan autoimmunity. Herein, we explore whether this is an intrinsic risk of xenothymus grafting or whether it depends on the transplant technique. We developed a new technique of "venous pouch" thymus grafting (heart-xenothymus) and compared this with the conventional kidney subcapsular technique (kidney-xenothymus) in a rat-into-nude-mouse model. Whereas lethal autoimmunity developed in 90% of kidney-xenothymus recipients, all heart-xenothymus grafted mice remained completely healthy. Autoimmunity in heart-xenothymus recipients was absent despite a significantly improved T-cell generation and was associated with significantly higher CD4(+)CD25(+) T-cell frequencies and CD4(+)CD25(+) cell Foxp3 mRNA levels than those observed in kidney-xenothymus recipients. In conclusion, we describe a novel vascular pouch technique of xenothymus transplantation that prevents the development of autoimmunity in nude mice. Our data further suggest that prevention of autoimmunity is related to a superior development of regulatory T-cells.