Alessandrini Alessandro, Turka Laurence A
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA.
Am J Kidney Dis. 2017 May;69(5):667-674. doi: 10.1053/j.ajkd.2016.10.027. Epub 2016 Dec 31.
Normal immune homeostasis is achieved by several mechanisms, and prominent among them is immunoregulation. Although several types of regulatory lymphocyte populations have been described, CD4 T cells expressing the FOXP3 transcription factor (FOXP3-positive regulatory T cells [FOXP3 Tregs]) are the best understood. This population of cells is critical for maintaining self-tolerance throughout the life of the organism. FOXP3 Tregs can develop within the thymus, but also under select circumstances, naive peripheral T cells can be induced to express FOXP3 and become stable Tregs as well. Abundant evidence from animal systems, as well as limited evidence in humans, implicates Tregs in transplant tolerance, although whether these Tregs recognize allo- or self-antigens is not clear. New translational approaches to promote immunosuppression minimization and/or actual tolerance are being designed to exploit these observations. These include strategies to boost the generation, maintenance, and stability of endogenous Tregs, as well as adoptive cellular therapy with exogenous Tregs.
正常的免疫稳态是通过多种机制实现的,其中突出的是免疫调节。虽然已经描述了几种类型的调节性淋巴细胞群体,但对表达FOXP3转录因子的CD4 T细胞(FOXP3阳性调节性T细胞[FOXP3 Tregs])的了解最为深入。这群细胞对于在生物体的整个生命过程中维持自身耐受性至关重要。FOXP3 Tregs可以在胸腺内发育,但在特定情况下,外周幼稚T细胞也可被诱导表达FOXP3并成为稳定的Tregs。来自动物系统的大量证据以及人类的有限证据表明Tregs与移植耐受有关,尽管这些Tregs识别的是同种异体抗原还是自身抗原尚不清楚。为利用这些观察结果,正在设计新的转化方法以促进免疫抑制最小化和/或实际耐受。这些方法包括促进内源性Tregs的产生、维持和稳定性的策略,以及外源性Tregs的过继性细胞治疗。