REVERSIBILITY OF CHRONIC RENAL ALLOGRAFT REJECTION: Critical Effect of Time After Transplantation Suggests Both Host Immune Dependent and Independent Phases of Progressive Injury1
REVERSIBILITY OF CHRONIC RENAL ALLOGRAFT REJECTION: Critical Effect of Time After Transplantation Suggests Both Host Immune Dependent and Independent Phases of Progressive Injury1
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慢性同种异体肾移植排斥的可逆性：移植后时间的关键影响表明进行性损伤的宿主免疫依赖性和独立阶段1
DOI：
10.1097/00007890-199407000-00016
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发表时间：
1994
期刊：
影响因子：
6.2
通讯作者：
N. Tilney
中科院分区：
文献类型：
--
作者：
S. Tullius;W. Hancock;U. Heemann;H. Azuma;N. Tilney
慢性排斥反应的同种异体肾移植发生肾小球硬化、间质纤维化和血管闭塞等特征性和进行性形态学改变，与功能下降和最终的移植物丧失直接相关。使用已建立的慢性排斥大鼠移植模型，其中这些变化以可预测的顺序发生，异体移植物在初始移植后以连续间隔重新移植回供体菌株，以确定在发育的哪个阶段仍然可以通过去除宿主的持续免疫驱动来逆转病变。形态学变化在相同的时间间隔内比较同种异体移植物和同种异体移植物再移植的形态学变化。慢性排斥反应的组织学和免疫组织学特征是可逆的，可在原肾放置后12周内再次移植到供体株中。在第12周或之后再次移植不能逆转强烈的体液和细胞免疫反应，也不能逆转这一时期后发生的结构变化（特别是纤维化）。然而，在再移植和非再移植的同种移植物对照中，稀疏但不可避免地进展的细胞浸润和细胞因子表达表明，除了宿主免疫的影响外，异体抗原非依赖性因素的持续影响。因此，慢性排斥反应的早期阶段是异体抗原依赖性和可逆性的，而后期的变化是不可逆的，异体抗原非依赖性因素显得越来越重要。
The characteristic and progressive morphological changes of glomerulosclerosis, interstitial fibrosis, and vascular obliteration that occur in renal allografts experiencing chronic rejection correlate directly with declining function and eventual graft loss. Using an established rat transplant model of chronic rejection where such changes occur in predictable sequence, allografts were retransplanted back into the donor strain at serial intervals after the initial engraftment to determine at what stage of development the lesions could still be reversed by removing the continuing immunological drive of the host. Morphological changes were compared with those in retransplanted isografts and nonretransplanted allografts at comparable time intervals. Histological and immunohistological characteristics of chronic rejection were reversible by retransplantation of the kidneys into the donor strain within 12 weeks after their original placement. Retransplantation at or later than week 12 could not reverse the intense humoral and cellular immune responses, or the structural changes (particularly fibrosis) that developed after that period. However, the sparse but inevitably progressing cellular infiltration and cytokine expression in retransplanted and nonretransplanted isograft controls suggest the persistent influence of alloantigen-independent factors in addition to those of host immunity. Thus, the early stages of chronic rejection are alloantigen dependent and reversible, whereas the later changes were irreversible and alloantigen-independent factors appeared increasingly important.