Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
Cold Spring Harb Perspect Med. 2013 Jun 1;3(6):a015545. doi: 10.1101/cshperspect.a015545.
Transplantation tolerance is a continuing therapeutic goal, and it is now clear that a subpopulation of T cells with regulatory activity (Treg) that express the transcription factor foxp3 are crucial to this aspiration. Although reprogramming of the immune system to donor-specific transplantation tolerance can be readily achieved in adult mouse models, it has yet to be successfully translated in human clinical practice. This requires that we understand the fundamental mechanisms by which donor antigen-specific Treg are induced and function to maintain tolerance, so that we can target therapies to enhance rather than impede these regulatory processes. Our current understanding is that Treg act via numerous molecular mechanisms, and critical underlying components such as mTOR inhibition, are only now emerging.
移植耐受是一个持续的治疗目标,现在很清楚,具有调节活性(Treg)的 T 细胞亚群表达转录因子 foxp3 对这一愿望至关重要。尽管在成年小鼠模型中可以很容易地对免疫系统进行重新编程以实现供体特异性移植耐受,但在人类临床实践中尚未成功转化。这就要求我们了解诱导供体抗原特异性 Treg 并维持耐受的基本机制,以便我们可以靶向治疗来增强而不是阻碍这些调节过程。我们目前的理解是,Treg 通过多种分子机制发挥作用,并且像 mTOR 抑制这样的关键基础成分现在才刚刚出现。