Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Medical Center Ulm and Center of Excellence Metabolic Disorders, Baden-Württemberg, Ulm, Germany.
J Leukoc Biol. 2010 May;87(5):943-8. doi: 10.1189/jlb.1109713.
Proinsulin is a major diabetes-associated autoantigen. APL have been shown to manipulate the immune response of T cells. Here, we generated a lysosomal protease-resistant proinsulin 74-90-derived APL using a CS-directed amino acid modification approach. These prAPL activated TGF-beta 1 secretion in proinsulin-reactive T cells from PBMC of patients with T1D. We provide evidence that proinsulin-derived prAPL modulate the cytokine signature of proinsulin-reactive T cells at a micromolar range by increasing anti-inflammatory cytokines, including TGF-beta 1. Thus, the use of prAPL is a promising tool to mitigate autoaggressive T cells.
胰岛素原是与糖尿病相关的主要自身抗原。已有研究表明，APL 可操纵 T 细胞的免疫反应。在此，我们采用 CS 指导的氨基酸修饰方法生成了一种溶酶体蛋白酶抗性的胰岛素原 74-90 衍生 APL。这些 prAPL 可激活 T1D 患者 PBMC 中胰岛素原反应性 T 细胞中 TGF-β1 的分泌。我们提供的证据表明，胰岛素原衍生的 prAPL 通过增加抗炎细胞因子（包括 TGF-β1）在微摩尔范围内调节胰岛素原反应性 T 细胞的细胞因子特征。因此，使用 prAPL 是减轻自身反应性 T 细胞的有前途的工具。
