Beschorner W E, Yao X, Divic J
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Transplantation. 1995 Dec 15;60(11):1326-30.
Based on studies of the thymic microenvironment in the model of cyclosporine (CsA)-associated syngeneic graft-versus-host disease, we have hypothesized that immune tolerance develops after CsA is stopped, as the thymus regenerates and recruits new dendritic cells. CsA normally induces medullary involution with destruction of the medullary dendritic cells (DC) and epithelium. This principle could provide practical advantages for transplantation if it is used to recruit new DC into the thymic medulla. Here we administer LEW x BN F1 splenocytes to BN rats and treat them with a short course of CsA. After CsA is stopped, the F1 cells are rapidly recruited to the thymus, and by 10 days after CsA, they are localized at the corticomedullary junction, the natural location of thymic DC. In contrast, dexamethasone, which induces cortical involution, did not lead to thymic recruitment of F1 DC. Recruitment was better if the splenocytes were administered before CsA was stopped. Engraftment of the thymus was also achieved using bone marrow and temporary skin grafts as sources of DC. These observations provide the basis for a novel approach to inducing tolerance to alloantigens with minimal immune suppression and define the goals for further development.
基于对环孢素（CsA）相关同基因移植物抗宿主病模型中胸腺微环境的研究，我们推测在停用CsA后，随着胸腺再生并募集新的树突状细胞，免疫耐受会得以发展。CsA通常会诱导髓质退化，破坏髓质树突状细胞（DC）和上皮细胞。如果将该原理用于向胸腺髓质募集新的DC，可能会为移植带来实际优势。在此，我们将LEW×BN F1脾细胞注射给BN大鼠，并用短疗程的CsA进行治疗。停用CsA后，F1细胞迅速被募集至胸腺，且在停用CsA后10天，它们定位于皮质髓质交界处，即胸腺DC的天然位置。相比之下，诱导皮质退化的地塞米松并未导致F1 DC向胸腺募集。若在停用CsA前注射脾细胞，则募集效果更佳。使用骨髓和临时皮肤移植物作为DC来源，也实现了胸腺植入。这些观察结果为一种以最小免疫抑制诱导对同种异体抗原耐受的新方法提供了依据，并明确了进一步发展的目标。
