THE INDUCTION OF SKIN-GRAFT TOLERANCE IN MAJOR HISTOCOMPATIBILITY COMPLEX-MISMATCHED OR PRIMED RECIPIENTS - PRIMED T-CELLS CAN BE TOLERIZED IN THE PERIPHERY WITH ANTI-CD4 AND ANTI-CD8 ANTIBODIES
THE INDUCTION OF SKIN-GRAFT TOLERANCE IN MAJOR HISTOCOMPATIBILITY COMPLEX-MISMATCHED OR PRIMED RECIPIENTS - PRIMED T-CELLS CAN BE TOLERIZED IN THE PERIPHERY WITH ANTI-CD4 AND ANTI-CD8 ANTIBODIES
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DOI：
10.1002/eji.1830201232
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发表时间：
1990-12-01
影响因子：
5.4
通讯作者：
WALDMANN, H
中科院分区：
文献类型：
--
作者：
COBBOLD, SP;MARTIN, G;WALDMANN, H
给予短程抗CD4和抗CD8单抗的小鼠开始对同时移植的同种异体皮肤产生耐受性。无论是在幼稚的动物还是在启动的动物中，都可以在不耗尽T细胞的情况下获得耐受性，无论是在幼稚的动物还是在启动的动物中，这表明即使外周T细胞已经被激活，它们也可以被耐受。在供体和受体在整个主要组织相容性复合体中不相容的情况下，可以通过联合使用耗竭和非耗竭抗体来实现特异性耐受，其中每种抗体单独使用都不成功。尽管小鼠对它们最初的皮肤移植明显耐受，但我们在一些菌株组合中观察到，第二种新鲜的、但基因相同的移植皮肤被缓慢排斥。这些小鼠还拥有T细胞，可以在体外增殖为供体类型的刺激细胞。无论是什么机制，我们已经证明，手术移植耐受可以通过简单、无毒的抗体治疗来实现。在临床器官移植中引入类似的诱导耐受方案可以消除长期免疫抑制的必要性及其不幸的副作用。
Mice given short courses of anti-CD4 and anti-CD8 monoclonal antibodies became tolerant of allogeneic skin grafted at the same time. Tolerance could be obtained without Tcell depletion across multiple minor antigen mismatches, both in naive and primed animals, demonstrating that peripheral T cells could be tolerized, even if they had been previously activated. Where donor and recipient were incompatible across the whole major histocompatibility complex, specific tolerance could be achieved by using a combination of depleting followed by non-depleting antibodies, where each alone was unsuccessful. Although mice clearly tolerated their original skin grafts, we observed in some strain combinations that a second fresh, but genotypically identical graft, was slowly rejected. Such mice also possessed T cells which could proliferate to donor-type stimulator cells in vitro. Whatever the mechanisms, we have demonstrated that operational transplantation tolerance can be achieved with simple, non-toxic antibody therapy. The introduction of comparable tolerance-inducing regimens in clinical organ transplantation could obviate the need for long-term immunosuppression and its unfortunate side effects.