BioDrugs. 2014 Feb;28(1):7-16. doi: 10.1007/s40259-013-0060-3.
Foxp3⁺ regulatory T (Treg) cells are critical contributors to the establishment and maintenance of immunological self-tolerance. Autoimmune type 1 diabetes (T1D) is characterized by the loss of self-tolerance to the insulin-producing β cells in the pancreas and the destruction of β cells, resulting in the development of chronic hyperglycemia at diagnosis. The application of strong agonistic T-cell receptor ligands provided under subimmunogenic conditions functions as a critical means for the efficient de novo conversion of naive CD4⁺ T cells into Foxp3⁺ Treg cells. The specific induction of Treg cells upon supply of strong-agonistic variants of certain self-antigens could therefore function as a critical instrument in order to achieve safe and specific prevention of autoimmunity such as T1D via the restoration of self-tolerance. Such immunotherapeutic strategies are being developed, and in the case of T1D aim to restrict autoimmunity and β-cell destruction. In this review, we discuss the requirements and opportunities for Treg-based tolerance approaches with the goal of interfering with autoimmune T1D.
Foxp3⁺ 调节性 T（Treg）细胞是建立和维持免疫自身耐受的关键贡献者。自身免疫性 1 型糖尿病（T1D）的特征是对胰腺中产生胰岛素的β细胞失去自身耐受性，导致β细胞破坏，从而在诊断时发展为慢性高血糖。在亚免疫条件下应用强激动性 T 细胞受体配体是将幼稚 CD4⁺ T 细胞有效转化为 Foxp3⁺ Treg 细胞的关键手段。因此，供应某些自身抗原的强激动性变体可特异性诱导 Treg 细胞，从而通过恢复自身耐受性，作为实现安全和特异性预防自身免疫（如 T1D）的关键手段。正在开发这种免疫治疗策略，在 T1D 的情况下，旨在限制自身免疫和β细胞破坏。在这篇综述中，我们讨论了基于 Treg 的耐受方法的要求和机会，以期干扰自身免疫性 T1D。
