Division of Cardiothoracic Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Curr Opin Organ Transplant. 2010 Feb;15(1):16-20. doi: 10.1097/MOT.0b013e3283342780.
We provide evidence for the role of de-novo development of immune responses to self-antigens in the posttransplant period and its possible induction by alloimmunity in the pathogenesis of chronic rejection following lung, heart and kidney transplantation. The present review details recent findings for the two distinct yet interdependent immune processes in the immunopathogenesis of chronic rejection.
The contribution of both humoral and cell-mediated alloimmune responses against mismatched donor histocompatibility antigens (HLA) in the pathogenesis of chronic rejection is well established. Recent studies have focused on development of immune responses to self-antigens during the posttransplant period and its correlation with chronic rejection. These self-antigens include myosin and vimentin in cardiac, K-alpha-1-tubulin and collagen-V in lung and angiotensin II type 1 receptor, collagen-IV and VI in kidney transplants. During the posttransplant period, the development of immune responses to self-antigens is facilitated by induction of a distinct subset of autoreactive T-helper cells referred to as Th17 cells.
Following organ transplantation, tissue injury and remodeling inflicted by antibodies (Abs) to HLA antigens is conducive to develop autoimmunity. Abs to HLA and self-antigens are detectable in the serum of transplant recipients who develop chronic rejection. Anti-HLA Abs are often present transiently but precede the development of Abs to self-antigens.
我们提供了在移植后时期内，自身抗原的新的免疫反应的发展及其在肺、心和肾移植后慢性排斥反应发病机制中可能由同种异体免疫诱导的证据。本综述详细介绍了慢性排斥反应免疫发病机制中两种截然不同但又相互依存的免疫过程的最新发现。
针对 mismatched donor histocompatibility antigens (HLA) 的体液和细胞介导的同种异体免疫反应在慢性排斥反应发病机制中的作用已得到充分证实。最近的研究集中在移植后时期内自身抗原免疫反应的发展及其与慢性排斥反应的相关性。这些自身抗原包括心脏中的肌球蛋白和波形蛋白、肺中的 K-alpha-1-微管蛋白和胶原-V 以及肾移植中的血管紧张素 II 型 1 受体、胶原-IV 和 VI。在移植后时期，自身反应性 T 辅助细胞（Th17 细胞）的诱导促进了对自身抗原免疫反应的发展。
在器官移植后，针对 HLA 抗原的抗体（Abs）造成的组织损伤和重塑有利于自身免疫的发展。在发生慢性排斥反应的移植受者的血清中可检测到抗-HLA 和自身抗原的 Abs。抗-HLA Abs 通常是短暂存在的，但先于自身抗原 Abs 的出现。
