Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Institutes of Medicine, HIM-730, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France; INSERM U1151, Institut Necker-Enfants Malades, 75015 Paris, France; CNRS UMR 8253, Institut Necker-Enfants Malades, 75015 Paris, France.
J Autoimmun. 2016 Jul;71:69-77. doi: 10.1016/j.jaut.2016.05.002. Epub 2016 May 21.
In this brief review we propose to discuss salient data showing the importance of immune regulatory mechanisms, and in particular of Treg, for the control of pathogenic anti-β-cell response in autoimmune diabetes. Disease progression that culminates with the massive destruction of insulin-secreting β-cells and advent of hyperglycemia and glycosuria tightly correlates with a functional deficit in immune regulation. Better dissection of the cellular and molecular mechanisms through which the immune system normally sustains tolerance to "self", and which become defective when autoimmune aggression is overt, is the only direct and robust way to learn how to harness these effectively, so as to restore immune tolerance in patients with insulin-dependent type 1 diabetes. No doubt that regulatory T cells are a privileged mechanism underlying this self-tolerance in the periphery. The discovery of the key role of the transcription factor FoxP3, represented the cornerstone leading to the great advances in the field we are witnessing today. Type 1 diabetes is certainly one of the prototypic T cell-mediated autoimmune diseases where immune regulatory mechanisms relying on specialized subsets of T cells have been the most thoroughly analyzed from the fundamental point of view and also largely exploited in a translational therapeutic perspective.
在这篇简要的综述中，我们拟讨论一些重要的数据，这些数据表明免疫调节机制，特别是 Treg，对于控制自身免疫性糖尿病中致病性抗β细胞反应的重要性。疾病的进展以胰岛素分泌β细胞的大量破坏以及高血糖和糖尿的出现为终点，这与免疫调节的功能缺陷密切相关。更好地剖析免疫系统通常维持对“自身”耐受的细胞和分子机制，以及当自身免疫攻击明显时这些机制变得有缺陷的机制，是了解如何有效地利用这些机制的唯一直接和可靠方法，以便在胰岛素依赖型 1 型糖尿病患者中恢复免疫耐受。毫无疑问，调节性 T 细胞是外周耐受的一个特权机制。转录因子 FoxP3 的关键作用的发现，代表了导致我们今天所见证的这一领域取得巨大进展的基石。1 型糖尿病无疑是 T 细胞介导的自身免疫性疾病的原型之一，从根本的角度来看，依赖于专门的 T 细胞亚群的免疫调节机制已经得到了最彻底的分析，并且在转化治疗的角度也得到了广泛的利用。
