First Hospital of Jilin University, Changchun, Jilin, China.
Xenotransplantation. 2010 Mar-Apr;17(2):160-5. doi: 10.1111/j.1399-3089.2010.00578.x.
We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, it remains unknown whether CD47 incompatibility also contributes to the rejection of non-hematopoietic xenografts.
Here, we investigated the role of CD47 in preventing macrophage-mediated rejection of thymic epithelial cells in a mouse model of thymic transplantation across the CD47 barrier.
Wild-type (WT) and CD47 KO mice were thymectomized and treated with T cell-depleting mAbs, and implanted with fetal thymus from syngeneic WT or CD47 KO donors.
Transplantation of CD47 KO mouse thymus led to T cell recovery in thymectomized, T cell-depleted WT mice. Similar to the control WT mouse thymic grafts, CD47 KO mouse thymic grafts showed a normal distribution of thymocyte subsets, and almost all of the thymocytes were recipient origin. Furthermore, histological analysis confirmed long-term survival of CD47 KO mouse thymic epithelial cells in WT mouse recipients.
These results demonstrate that, unlike hematopoietic cells, CD47 KO mouse thymus can survive and function in WT mice. Furthermore, our data implicate that the role of CD47 in xenograft rejection may differ for different types of xenografts, and that CD47 incompatibility is unlikely to impede thymic xenotransplantation, a potential approach to inducing xenotolerance, by triggering macrophage-mediated rejection.
我们之前已经表明，CD47 的种间不相容性在触发巨噬细胞对异种造血细胞的排斥反应中起着重要作用。然而，目前尚不清楚 CD47 不相容性是否也有助于排斥非造血异种移植物。
本研究旨在探讨 CD47 在预防巨噬细胞介导的异种胸腺上皮细胞排斥反应中的作用，建立了跨越 CD47 屏障的异种胸腺移植小鼠模型。
对野生型（WT）和 CD47 KO 小鼠进行胸腺切除术，并接受 T 细胞耗竭 mAb 治疗，然后植入来自同基因 WT 或 CD47 KO 供体的胎胸腺。
CD47 KO 小鼠胸腺移植导致胸腺切除、T 细胞耗竭的 WT 小鼠中 T 细胞恢复。与对照 WT 小鼠胸腺移植物类似，CD47 KO 小鼠胸腺移植物显示出正常的胸腺细胞亚群分布，并且几乎所有的胸腺细胞均来自受者。此外，组织学分析证实 CD47 KO 小鼠胸腺上皮细胞在 WT 小鼠受者中可长期存活。
这些结果表明，与造血细胞不同，CD47 KO 小鼠胸腺可在 WT 小鼠中存活并发挥功能。此外，我们的数据表明，CD47 在异种移植物排斥中的作用可能因不同类型的异种移植物而异，并且 CD47 不相容性不太可能通过触发巨噬细胞介导的排斥反应来阻碍胸腺异种移植，这是一种诱导异种免疫耐受的潜在方法。
