Transgenic mice : a unique model to reassess specific T cell suppression

移植器官的接受目前是通过使用阻断T细胞反应的免疫抑制药物治疗受体来实现的。然而，由于这些药物是非特异性的，它们会阻断所有的T细胞反应，包括那些针对不受欢迎的病毒或细菌感染的反应。所以，虽然这个策略是目前最好的，但它远非理想的。最好的治疗方法是在不抑制免疫的情况下诱导特异性移植物接受。在20世纪70年代，几项研究描述了由T淋巴细胞亚群介导的受体实现特异性抑制的治疗。虽然可以观察到这种现象，但对于解释不同模型中涉及的机制尚未达成共识。其中一个原因是无法追踪抑制性T细胞群。我们现在有了技术和更多的知识来重新评估这些研究，并了解如何实现特异性抑制。我们实验室开发了转基因小鼠来研究这些现象。我们的一个转基因模型模拟了肝移植后的T细胞反应。肝移植比其他器官移植更容易被接受，即使跨越主要的组织相容性（MHC）屏障和不使用免疫抑制药物。肝移植不仅被广泛接受，而且还可能引起对来自同一供者的肾脏或心脏移植的二次接受，否则这些移植会被排斥。尽管外科医生已经利用了这一特性，但肝脏被接受和诱导接受其他器官的惊人能力仍然不为人所知。先前的研究和我们自己的模型表明，这与特异性抑制有关。我们的模型使我们能够跟踪相关细胞，因此提供了一种独特的工具来了解如何实现特定的抑制。了解这些机制将有助于我们设计策略来诱导对任何器官的耐受性而不抑制患者的免疫。

Acceptance of transplanted organs is currently achieved by treating the recipient with immunosuppressive drugs that block T cell responses. However, because these drugs are non-specific, they will block all T cell responses, including those directed to undesirable viral or bacterial infections. So, whilst this strategy is the best available at the moment, it is far from ideal. The best treatment would be to induce specific graft acceptance without immunosuppression. In the 1970 s several studies have described treatment of recipients achieving specific suppression mediated by a subset of T lymphocytes. Although the phenomenon can be observed, no consensus has been reached to explain the mechanisms involved in the different models. One reason was the unability to track a population of suppressive T cells. We have now the technology and more knowledge to reassess these studies and understand how specific suppression can be achieved. Our lab has developed transgenic mice to study these phenomenon. One of our transgenic models mimicks the T cell response following liver transplantation. Acceptance of liver transplants is more readily achieved than to other organ grafts, even across a major histocompatibility (MHC) barrier and without immunosuppressive drugs. Not only are liver transplants well accepted, but they may induce secondary acceptance of kidney or heart grafts from the same donor, which would otherwise be rejected. Although this property has been made use of by surgeons, the amazing capacity of the liver to be accepted and to induce acceptance of other organs is still not understood. Previous studies and our own model suggests that specific suppression is involved. Our model which enable us to track the relevant cells provides therefore a unique tool to understand how specific suppression can be achieved. Understanding these mechanisms would help us to design strategies to induce tolerance to any organ without immunosuppressing the patient.