Mauvais François-Xavier, Diana Julien, van Endert Peter
Institut National de la Santé et de la Recherche Médical, Unité 1151, Paris, 75015, France; Centre National de la Recherche Scientifique, UMR8253, Paris, 75015, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, 75015, France.
F1000Res. 2016 Apr 22;5. doi: 10.12688/f1000research.7411.1. eCollection 2016.
Research focusing on type 1 diabetes (T1D) autoantigens aims to explore our understanding of these beta cell proteins in order to design assays for monitoring the pathogenic autoimmune response, as well as safe and efficient therapies preventing or stopping it. In this review, we will discuss progress made in the last 5 years with respect to mechanistic understanding, diagnostic monitoring, and therapeutic modulation of the autoantigen-specific cellular immune response in T1D. Some technical progress in monitoring tools has been made; however, the potential of recent technologies for highly multiplexed exploration of human cellular immune responses remains to be exploited in T1D research, as it may be the key to the identification of surrogate markers of disease progression that are still wanting. Detailed analysis of autoantigen recognition by T cells suggests an important role of non-conventional antigen presentation and processing in beta cell-directed autoimmunity, but the impact of this in human T1D has been little explored. Finally, therapeutic administration of autoantigens to T1D patients has produced disappointing results. The application of novel modes of autoantigen administration, careful translation of mechanistic understanding obtained in preclinical studies and in vitro with human cells, and combination therapies including CD3 antibodies may help to make autoantigen-based immunotherapy for T1D a success story in the future.
聚焦于1型糖尿病（T1D）自身抗原的研究旨在探索我们对这些β细胞蛋白的理解，以便设计用于监测致病性自身免疫反应的检测方法，以及预防或阻止该反应的安全有效的疗法。在本综述中，我们将讨论过去5年在T1D自身抗原特异性细胞免疫反应的机制理解、诊断监测和治疗调节方面取得的进展。在监测工具方面已经取得了一些技术进步；然而，近期用于高度多重探索人类细胞免疫反应的技术潜力在T1D研究中仍有待挖掘，因为这可能是识别仍缺失的疾病进展替代标志物的关键。对T细胞识别自身抗原的详细分析表明，非传统抗原呈递和加工在β细胞定向自身免疫中起重要作用，但这在人类T1D中的影响尚未得到充分探索。最后，向T1D患者进行自身抗原的治疗性给药产生了令人失望的结果。应用新型自身抗原给药模式、仔细转化在临床前研究和体外用人细胞获得的机制理解，以及包括CD3抗体在内的联合疗法，可能有助于使基于自身抗原的T1D免疫疗法在未来成为一个成功案例。
