Contribution of early acute rejection episodes to chronic rejection in a rat kidney retransplantation model
Contribution of early acute rejection episodes to chronic rejection in a rat kidney retransplantation model
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DOI：
10.1046/j.1523-1755.1998.00757.x
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发表时间：
1998-02-01
影响因子：
19.6
通讯作者：
Tilney, NL
中科院分区：
文献类型：
--
作者：
Tullius, SG;Nieminen, M;Tilney, NL
慢性移植物排斥反应是器官移植后长期效果不满意的最重要的危险因素。除了各种同种异体抗原依赖性和独立性因素外，急性排斥反应事件已被引用为主要的免疫风险因素。然而，急性排斥反应对移植物长期预后的影响仍不清楚。为了研究单个早期排斥事件对最终移植结果的影响，将急性排斥大鼠肾移植物按顺序重新移植到同系大鼠中，并随时间评估其功能和结构行为。在3、4、5和7天后（N = 12/组/时间段）从LEW受体中取出LEWxBNF（1）肾同种异体移植物和LEW同种异体移植物，并重新移植到供体品系宿主中。移植物功能随访，并在4周、8周和32周后收获。每周测定尿蛋白排泄量。使用抗巨噬细胞（艾德-1）、T细胞及其亚群（CD 5、CD 4、CD 8）、MHC II类表达（OX 3）和粘附分子（ICAM-1和LFA-1 α）的单克隆抗体（mAb）对肾脏进行形态学和免疫组织学检查。非再次移植同种异体移植物的平均标准时间± 2天为14.5 ± 2天;同种异体移植物无限期发挥功能。在第5天和第7天，急性排斥反应的同种异体移植物显示大量细胞浸润和广泛坏死。这些变化不能通过再次移植逆转，同基因受体后来死于肾功能衰竭。相比之下，大多数早期再移植的同种异体移植物在3天（12/12例同种异体移植物）和4天（7/12例同种异体移植物）后完全恢复。在随后的随访期间，再次移植的同种异体移植物和同种异体移植物的尿蛋白排泄量相当。在再次移植后的随访期间，仅偶尔观察到在第3天和第4天非再次移植的同种异体移植物中单核细胞浸润增加。到32周时，仅观察到少数硬化肾小球（类似于15%）、轻度动脉变化和最小细胞浸润，这与再次移植的同种移植物中观察到的相似。一个单一的急性排斥反应事件是完全可逆的，并没有进展到慢性排斥反应，如果再次移植到同基因供体时，炎症变化仍然是早期的。这些结果证明了同种异体抗原依赖性事件对慢性移植物恶化的关键作用，并表明对初始急性排斥反应事件进行及时和积极的治疗有利于防止移植物中的晚期有害变化。
Chronic graft rejection represents the single most important risk factor for unsatisfactory long-term results after organ transplantation. In addition to various alloantigen dependent and independent factors, acute rejection episodes have been cited as a major immunological risk factor. However, the effects of acute rejection episodes on long-term graft outcome remains unknown. To examine the influence of a single early rejection event on ultimate graft outcome, acutely rejecting rat kidney grafts were retransplanted sequentially into syngeneic rats and their functional and structural behavior assessed over time. LEWxBNF(1) kidney allografts and LEW isografts were removed from their LEW recipients after three, four, five and seven days (N = 12/group/time period) and retransplanted into donor strain hosts. The grafts were followed functionally and harvested four, eight, and 32 weeks later. Urinary protein excretion was measured weekly. Kidneys were examined morphologically and immunohistologically using monoclonal antibodies (mAbs) against macrophages (ED-1), T cells and their subsets (CD5, CD4, CD8), MHC class II expression (OX3) and adhesion molecules (ICAM-1 and LFA-1 alpha). The mean standard time +/- so of non-retransplanted allografts was 14.5 +/- two days; isografts functioned indefinitely. At five and seven days, acutely rejecting allografts showed massive cellular infiltrates associated with extensive necrosis. These changes could not be reversed by retransplantation and the syngeneic recipients later died of renal failure. In contrast, most allografts retransplanted earlier in the process recovered completely when retransplanted after three (12 of 12 allografts) and four (7 of 12 allografts) days. During the subsequent follow-up period, urinary protein excretion was comparable in retransplanted allografts and isografts. The increased mononuclear cell infiltration in non-retransplanted allografts seen at three and four days was only occasionally observed during the follow-up period after retransplantation. Only a few sclerosed glomeruli (similar to 15%), mild arterial changes and minimal cellular infiltrates were observed by 32 weeks, which were similar to that seen in retransplanted isografts. A single acute rejection episode was completely reversible and did not progress to chronic rejection if retransplanted into syngeneic donors when the inflammatory changes are still early. Those results demonstrate the critical effect of alloantigen-dependent events on chronic graft deterioration, and indicate that prompt and aggressive treatment of initial acute rejection episodes are beneficial to protect against late deleterious changes in the graft.