GRAFT ADAPTATION - STUDIES ON POSSIBLE MECHANISMS IN LONG-TERM SURVIVING RAT RENAL-ALLOGRAFTS

GRAFT ADAPTATION - STUDIES ON POSSIBLE MECHANISMS IN LONG-TERM SURVIVING RAT RENAL-ALLOGRAFTS
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DOI:
10.1097/00007890-198007000-00016
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发表时间:
1980-01-01
期刊:
影响因子:
6.2
通讯作者:
FABRE, JW
FABRE, JW
中科院分区:
医学2区
文献类型:
--
作者:
HART, DNJ;WINEARLS, CG;FABRE, JW

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将长期存活(100-120天)的肾同种异体移植物以3种供体-受体组合重新移植到与原始宿主同基因的新鲜受体:DA至LEW、(DA×LEW)F1至LEW和(DA×LEW)F1至DA。 3种组合的结果明显不同。 DA 至 LEW 模型中长期存活的移植物与新鲜移植物一样被强烈排斥。在 F1 至 DA 模型中,它们无限期存活,在任何阶段都没有任何移植功能损害。在 F1 至 LEW 模型中,大多数移植物经历了急性排斥反应,但大多数恢复并在移植物功能受损的情况下长期存活。 DA 至 LEW 和 F1 至 LEW 模型中长期存活的移植物几乎完全不能诱导淋巴细胞毒素反应,这与使用新鲜肾移植物所见的强烈反应形成鲜明对比。通过三种方式检查移植物适应机制。对来自 LEW 宿主的 6 个长期存活的 DA 和 4 个长期存活的 F1 肾脏中的每一个进行的定量吸收分析表明,不相容的 RT-1B (Ia) 抗原的量正常,而不相容的 RT-1A (SD) 抗原的量增加了 3 倍。这些结果排除了抗原调节和抗原掩蔽作为适应机制。通过证明长期存活的 DA 肾移植物可以通过注射同种抗血清和补体进行超急性排斥,排除了移植物内皮被宿主内皮替代的可能性。通过在移植时注射供体血液来替换过客白细胞的尝试没有成功。
Long-term surviving (100-120 days) renal allografts were retransplanted to fresh recipients syngeneic with the original host in 3 donor-recipient combinations: DA to LEW, (DA .times. LEW)F1 to LEW and (DA .times. LEW)F1 to DA. The results were markedly different in the 3 combinations. Long-term surviving grafts in the DA to LEW model were rejected as vigorously as fresh grafts. In the F1 to DA model they survived indefinitely without any impairment of graft function at any stage. In the F1 to LEW models most grafts underwent acute rejection but most recovered to survive for prolonged periods with impaired graft function. Long-term surviving grafts in the DA to LEW and F1 to LEW models were almost completely unable to induce lymphocytotoxin responses in marked contrast to the strong responses seen with the use of fresh kidney grafts. The mechanism of graft adaptation was examined in 3 ways. Quantitative absorption analysis on each of 6 long-term surviving DA and 4 long-term surviving F1 kidneys from LEW hosts showed that the amount of incompatible RT-1B (Ia) antigens was normal whereas the amount of incompatible RT-1A (SD) antigen was increased by a factor of 3. These results excluded antigen modulation and antigen masking as the mechanism of adaptation. The possibility that graft endothelium is replaced by host endothelium was excluded by showing that long-term surviving DA kidney grafts could be hyperacutely rejected by injecting alloantisera and complement. Attempts to replace passenger leukocytes by injecting donor blood at the time of grafting were not successful.