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

在攻击之前，免疫系统同样能够以强大的自我维持耐受性或建立破坏性反应来响应新抗原;免疫系统根据遇到抗原的背景来决定最适当的反应。然而，一旦系统向破坏性反应或耐受性崩溃，适应性反应被启动，它就会致力于这个决定。其中存在两个最大的障碍，以长期移植物的接受：不可避免的炎症与实体器官移植，和存在的T细胞记忆的同种异体抗原。类似地，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。从这个角度来看，它遵循围移植免疫反应的控制和接受者对移植物接受反应的教育可能会积极影响移植的长期结果。临床研究单位的目的是了解早期免疫因素如何决定移植物的长期成功。为此，我们工作组的研究将针对两个可能影响移植结果的主要免疫学方面，即受体先天性和适应性免疫反应。非特异性先天识别机制在形成对同种异体移植组织的非常早期的反应，建立最终导致慢性同种异体移植物相关病理的后果链中特别重要。证明这种应答的是关键细胞类型的效应子和调节子之间的平衡，包括T细胞、B细胞、NK细胞和巨噬细胞。从我们的临床研究单位研究先天和适应性细胞和体液免疫反应获得的信息的整合，预计将揭示新的见解，免疫因素是形成有利的，而不是穷人，同种异体移植结果的关键。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病理性移植后同种异体反应性，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.