Prevention Of Chronic Rejection And Graft Arteriosclerosis By Tolerance Induction
Prevention Of Chronic Rejection And Graft Arteriosclerosis By Tolerance Induction
复制标题
通过耐受诱导预防慢性排斥反应和移植物动脉硬化
DOI：
10.1097/00007890-199501000-00022
复制
发表时间：
1995
期刊：
影响因子：
6.2
通讯作者：
S. Jordan
中科院分区：
文献类型：
--
作者：
M. Orloff;E. DeMara;M. Coppage;N. Leong;M. Fallon;J. Sickel;X. Zuo;J. Prehn;S. Jordan
慢性排斥反应是实体器官移植第一年后移植失败的主要原因。各种慢性排斥器官的特征性病变是纤维内膜增生性动脉硬化。据推测，诱导耐受的方法可能不仅在避免急性排斥方面有效，而且在慢性排斥方面也是有效的。从Lewis-to-F-344品系的大鼠移植的心脏自然出现了慢性排斥反应的画面。我们研究了在已建立的慢性排斥模型中，通过骨髓移植诱导耐受和发展造血细胞嵌合体或胸腺内接种同种异体抗原诱导耐受是否能有效地预防慢性排斥反应。用去T细胞异基因骨髓(TCD A BMT)移植在F-344宿主体内形成骨髓嵌合体。另一组F-344宿主被胸腺内接种异基因骨髓细胞。这些动物的心脏移植在移植后120天内表现出耐受性。对照组F-344动物接受短程环孢素治疗后，在心脏移植后120天内持续出现慢性排斥反应。令人惊讶的是，耐受组动物中没有任何移植物动脉硬化的迹象，而绝大多数对照组动物都表现出了这一点。心脏移植后30天的细胞因子信使核糖核酸分析显示，对照组和耐受组动物之间存在差异。这些结果表明，耐受诱导能有效预防慢性排斥反应。
Chronic rejection is a major cause of graft failure in solid organ transplants after the first year. A characteristic lesion in a variety of chronically rejecting organs is a fibrointimal proliferative arteriosclerosis. It has been speculated that approaches to tolerance induction may be effective in obviating not only acute, but also chronic, rejection. A picture of chronic rejection develops naturally in heart grafts transplanted from the Lewis-to-F-344 strain of rat. We examined whether tolerance induction by bone marrow transplantation and development of hematopoietic chimerism or tolerance induction by intrathymic inoculation of alloantigen could effectively prevent chronic rejection in an established model of chronic rejection. Bone marrow chimeras were developed in F-344 hosts by transplantation of T cell-depleted allogeneic marrow (TCD A BMT). Another set of F-344 hosts was inoculated with intrathymic allogeneic bone marrow cells. Heart grafts in these animals demonstrated tolerance for 120 days after transplantation. Control F-344 animals treated with a short course of cyclosporine consistently developed chronic rejection by 120 days following heart transplantation. Strikingly absent from the tolerant animals was any sign of graft arteriosclerosis, which was demonstrated in the vast majority of control animals. Analysis of cytokine mRNA profiles at 30 days following heart transplantation demonstrated differences between control and tolerant animals. These results suggest that tolerance induction can effectively prevent chronic rejection.