CYCLOSPORIN-A, A POWERFUL IMMUNOSUPPRESSANT INVIVO AND INVITRO IN THE DOG, FAILS TO INDUCE TOLERANCE
CYCLOSPORIN-A, A POWERFUL IMMUNOSUPPRESSANT INVIVO AND INVITRO IN THE DOG, FAILS TO INDUCE TOLERANCE
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DOI：
10.1097/00007890-198003000-00014
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发表时间：
1980-01-01
期刊：
影响因子：
6.2
通讯作者：
THOMAS, ED
中科院分区：
文献类型：
--
作者：
DEEG, HJ;STORB, R;THOMAS, ED
环孢菌素A（Cy A）在狗中进行了评价，以观察其在延长DLA不相同、无关供体皮肤移植物存活和逆转排斥反应危象方面的有效性。CyA在21天的疗程中给予。采用混合白细胞培养物（MLC）和间接细胞介导的淋巴细胞溶解（CML）对犬进行体外监测。移植物在整个第一个Cy A疗程中保持活力。在第27-33天出现排斥迹象。4只狗中的3只通过第二个疗程的Cy A逆转了这些情况。第二次和第三次排斥反应的危机后，随后的课程的环孢素A也被逆转。在停止Cy A后，第一组移植物最终在第83-114天被排斥。第二组移植物存活也延长了Cy A和排斥反应的危机逆转了额外的Cy A课程。停用Cy A后，第二组移植物发生排斥反应。第一组35只未治疗犬的中位移植物存活时间为12天，第二组（24只犬）为8天。当在正常血清中建立时，所有Cy A治疗犬的淋巴细胞在MLC和CML中对皮肤移植供体和无关犬的淋巴细胞显示正常反应性。在Cy A处理的狗的血清中，MLC和CML反应性被消除。在体外加入Cy A时观察到类似的抑制。有丝分裂原诱导的胚细胞生成被Cy A处理的狗的血清轻度抑制。Cy A在体内和体外对狗来说是一种强大的免疫抑制剂，但无法诱导持续的免疫无反应。免疫抑制似乎取决于药物的持续存在。
Cyclosporin A (Cy A) was evaluated in dogs for its effectiveness in prolonging skin graft survival from DLA-nonidentical, unrelated donors and in reversing rejection crises. Cy A was given in courses of 21 days. Dogs were monitored in vitro with mixed leukocyte cultures (MLC) and indirect cell-mediated lympholysis (CML). Grafts remained viable throughout the first Cy A course. Signs of rejection developed on days 27-33. These were reversed in 3 of 4 dogs by a 2nd course of Cy A. Second and third rejection crises following subsequent courses of Cy A were also reversed. After stopping Cy A 1st-set grafts were ultimately rejected, by days 83-114. Second-set graft survival was also prolonged by Cy A and rejection crises were reversed by additional Cy A courses. After stopping Cy A 2nd-set grafts were rejected. Median graft survival in 35 untreated dogs was 12 days for the 1st and 8 days for the 2nd set (24 dogs). Lymphocytes from all Cy A-treated dogs showed normal reactivity in MLC and CML against lymphocytes from skin graft donors and unrelated dogs when set up in normal serum. In serum from Cy A-treated dogs, MLC and CML reactivities were abrogated. Similar suppression was seen with Cy A added in vitro. Mitogen-induced blastogenesis was mildly suppressed by serum from Cy A-treated dogs. Cy A is a powerful immunosuppressant in the dog in vivo and in vitro but fails to induce persistent immunological unresponsiveness. Immunosuppression appears to depend upon the continued presence of the drug.