KFO 243: Early Immunological Determinants of Late Transplant Outcome (ELITE)

在挑战之前，免疫系统同样有能力对新的抗原做出反应，具有强大的自我持久耐受性，或发起破坏性反应；免疫系统根据遇到抗原的背景决定最合适的反应。然而，一旦系统朝着破坏性反应或容忍崩溃，适应性反应被启动，那么它就会致力于做出这一决定。这就是长期接受移植物的两个最大障碍：与实体器官移植相关的不可避免的炎症，以及同种异体抗原T细胞记忆的存在。同样，适当调节的免疫系统的重建对于成功的骨髓移植是必不可少的。从这一观点来看，移植围术期对免疫反应的控制和对受者对移植接受的反应的教育可能会对移植的长期结果产生积极影响。临床研究单位的目的是了解早期免疫因素如何决定同种异体移植的长期成功。出于这个目的，我们工作组的研究将针对可能影响移植结果的两个主要免疫学方面，即接受者的先天免疫反应和获得性免疫反应。非特定的先天识别机制在形成对同种异体移植组织的早期反应方面特别重要，建立了最终导致慢性同种异体移植相关病理的后果链。协调这一反应的是T细胞、B细胞、NK细胞和巨噬细胞等关键细胞类型的效应子和调节子之间的平衡。从研究先天和获得性细胞和体液免疫反应中获得的信息整合在我们的临床研究单位内，预计将揭示哪些免疫因素在形成有利的同种异体移植结果方面起关键作用。通过更全面地了解这些复杂的早期事件，我们希望开发新的治疗策略来控制和监测移植后的病理同种异体反应，从而改善长期移植结果。

Prior to challenge, the immune system is equally capable of responding to a novel antigen with a robust self-perpetuating tolerance, or mounting a destructive reaction; the immune system decides upon the most appropriate response depending on the context in which the antigen is encountered. However, once the system has collapsed towards either destructive reaction or tolerance, and the adaptive response is primed, then it becomes committed to that decision. Therein lie the two greatest obstacles to long-term graft acceptance: the inevitable inflammation associated with solid organ transplantation, and the existence of T cell memory for alloantigen. Similarly, the reconstitution of a properly regulated immune system is essential for successful bone marrow engraftment. From this view, it follows that peritransplant control of immunological reactions and education of recipients responses towards graft acceptance might positively influence long-term outcomes in transplantation. The aim of the Clinical Research Unit is to understand how early immunologic factors determine long-term allograft success. With this purpose, research from our workgroups will be directed towards two principal immunologic aspects that are likely to affect transplant outcome, namely recipient innate and adaptive immune responses. Non-specific innate recognition mechanisms are particularly important in shaping very early reactions to allogeneic transplanted tissues, establishing the chain of consequences that ultimately results in chronic allograft-related pathology. Orchestrating this response is the balance between effector and regulatory subsets of key cell types, including T cells, B cells, NK cells and macrophages. The integration of information obtained from studying both the innate and adaptive cellular and humoral immune responses within our Clinical Research Unit is expected to reveal new insights into which immunological factors are critical in forming favourable, versus poor, allogeneic transplant outcomes. By understanding these complex early events more fully, we hope to develop novel therapeutic strategies to control and monitor pathologic posttransplant alloreactivity, thereby improving long-term transplant outcome.