Tullius S G, Hancock W W, Heemann U, Azuma H, Tilney N L
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.
Transplantation. 1994 Jul 15;58(1):93-9.
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 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.
在经历慢性排斥反应的肾移植中出现的肾小球硬化、间质纤维化和血管闭塞等特征性且进行性的形态学变化，与肾功能下降及最终移植肾丢失直接相关。利用已建立的大鼠慢性排斥反应移植模型（在此模型中此类变化按可预测的顺序发生），在初次植入后按连续间隔将移植肾重新移植回供体品系，以确定在发育的哪个阶段通过消除宿主持续的免疫驱动仍可逆转病变。将形态学变化与在可比时间间隔下重新移植的同基因移植肾和未重新移植的同种异体移植肾中的变化进行比较。慢性排斥反应的组织学和免疫组织学特征在第12周或之后重新移植时是可逆的，但无法逆转在此期间之后出现的强烈体液和细胞免疫反应或结构变化（尤其是纤维化）。然而，在重新移植和未重新移植的同基因移植肾对照中稀疏但不可避免进展的细胞浸润和细胞因子表达表明，除了宿主免疫因素外，同种异体抗原非依赖性因素也持续产生影响。因此，慢性排斥反应的早期阶段是同种异体抗原依赖性且可逆的，而后期变化是不可逆的，并且同种异体抗原非依赖性因素显得越来越重要。
