Autoimmunity against pancreatic β-cell autoantigens is a characteristic of childhood type 1 diabetes (T1D). Autoimmunity usually appears in genetically susceptible children with the development of autoantibodies against (pro)insulin in early childhood. The offspring of mothers with T1D are protected from this process. The aim of this study was to determine whether the protection conferred by maternal T1D is associated with improved neonatal tolerance against (pro)insulin. Consistent with improved neonatal tolerance, the offspring of mothers with T1D had reduced cord blood CD4+ T-cell responses to proinsulin and insulin, a reduction in the inflammatory profile of their proinsulin-responsive CD4+ T cells, and improved regulation of CD4+ T cell responses to proinsulin at 9 months of age, as compared with offspring with a father or sibling with T1D. Maternal T1D was also associated with a modest reduction in CpG methylation of the INS gene in cord blood mononuclear cells from offspring with a susceptible INS genotype. Our findings support the concept that a maternal T1D environment improves neonatal immune tolerance against the autoantigen (pro)insulin.

中文翻译：

---

母体 1 型糖尿病减少后代的自身抗原反应性 CD4+ T 细胞

针对胰腺 β 细胞自身抗原的自身免疫是儿童 1 型糖尿病 (T1D) 的特征。自身免疫通常出现在遗传易感儿童中，在儿童早期会产生针对（原）胰岛素的自身抗体。患有 T1D 的母亲的后代不受此过程的影响。本研究的目的是确定母体 T1D 赋予的保护是否与提高新生儿对（原）胰岛素的耐受性有关。与改善的新生儿耐受性一致，患有 T1D 的母亲的后代降低了脐带血 CD4+ T 细胞对胰岛素原和胰岛素的反应，降低了其胰岛素原反应性 CD4+ T 细胞的炎症特征，并改善了 CD4+ T 细胞对胰岛素原和胰岛素反应的调节。与父亲或兄弟姐妹患有 T1D 的后代相比，9 个月大时的胰岛素原。母体 T1D 还与来自具有易感 INS 基因型的后代的脐带血单核细胞中 INS 基因的 CpG 甲基化的适度减少有关。我们的研究结果支持母体 T1D 环境改善新生儿对自身抗原（原）胰岛素的免疫耐受性的概念。