Autoantibodies (AAbs) are a hallmark of Type 1 diabetes (T1D). Alterations in the frequency and phenotype of follicular helper (Tfh) T cells have been previously documented in patients with type 1 diabetes (T1D), but the contribution of follicular regulatory T (Treg) cells, which are responsible for suppressing AAb development, is less clear. Here, we investigated the frequency and activation status of follicular (CXCR5+) and conventional (CXCR5-) Treg cells in the blood of children with new-onset T1D, and children with risk for developing T1D (AAb-positive) and compared them to AAb-negative controls. Blood follicular and conventional Treg cells were higher in frequency in children with new onset T1D, but expressed reduced amounts of PD-1 as compared to AAb-negative children. Interestingly, the proportion of circulating FOXP3+ Tregs expressing PD-1 was also reduced in AAb-positive at-risk children as compared to AAb-negative controls, suggesting its potential use as a biomarker of disease progression. Follicular Treg cells were reduced in frequency in the spleens of prediabetic NOD mice as they became older and turned diabetic. Interestingly, PD-1 expression declined also on circulating follicular and conventional Treg cells in prediabetic NOD mice as they aged. Together, these findings show that the frequency of circulating follicular and conventional Treg cells and their levels of PD-1 change with disease progression in children at-risk for developing T1D and in NOD mice.

中文翻译：

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新发1型糖尿病儿童和自身抗体阳性高危儿童的循环卵泡和常规FOXP3 + Treg细胞中PD-1的表达降低。

自身抗体（AAb）是1型糖尿病（T1D）的标志。先前已在1型糖尿病（T1D）患者中记录了滤泡辅助性（Tfh）T细胞的频率和表型改变，但负责抑制Aab发育的滤泡性调节性T（Treg）细胞的贡献却较少。清除。在这里，我们调查了新发T1D患儿和有发展成T1D风险（AAb阳性）的儿童血液中卵泡（CXCR5 +）和常规（CXCR5-）Treg细胞的频率和激活状态，并将其与AAb进行了比较-阴性对照。新发T1D患儿的血滤泡细胞和常规Treg细胞的频率更高，但与AAb阴性儿童相比，PD-1的表达减少。有趣的是，与Abb阴性对照相比，AAb阳性高危儿童中循环表达PD-1的FOXP3 + Tregs的比例也降低，表明其潜在用途可作为疾病进展的生物标志物。糖尿病前期NOD小鼠脾脏中滤泡性Treg细胞的频率降低，因为它们变老并变成糖尿病。有趣的是，随着年龄的增长，糖尿病前期NOD小鼠的循环卵泡细胞和常规Treg细胞中PD-1的表达也下降。在一起，这些发现表明，在发育中的T1D患儿和NOD小鼠中，循环的卵泡细胞和常规Treg细胞的频率及其PD-1的水平随疾病的进展而变化。糖尿病前期NOD小鼠的脾脏中滤泡性Treg细胞的频率降低，因为它们变老并变成糖尿病。有趣的是，随着年龄的增长，糖尿病前期NOD小鼠的循环卵泡细胞和常规Treg细胞中PD-1的表达也下降。在一起，这些发现表明，在发育中的T1D患儿和NOD小鼠中，循环的卵泡细胞和常规Treg细胞的频率及其PD-1的水平随疾病的进展而变化。糖尿病前期NOD小鼠脾脏中滤泡性Treg细胞的频率降低，因为它们变老并变成糖尿病。有趣的是，随着年龄的增长，糖尿病前期NOD小鼠的循环卵泡细胞和常规Treg细胞中PD-1的表达也下降。在一起，这些发现表明，在发育中的T1D患儿和NOD小鼠中，循环的卵泡细胞和常规Treg细胞的频率及其PD-1的水平随疾病的进展而变化。