Circulating CXCR5-PD-1hi peripheral T helper cells are associated with progression to type 1 diabetes
Circulating CXCR5-PD-1hi peripheral T helper cells are associated with progression to type 1 diabetes
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DOI：
10.1007/s00125-019-4936-8
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发表时间：
2019-09-01
期刊：
影响因子：
8.2
通讯作者：
Kinnunen, Tuure
中科院分区：
文献类型：
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作者：
Ekman, Ilse;Ihantola, Emmi-Leena;Kinnunen, Tuure
目的/假设1型糖尿病之前有一段时间的无症状自身免疫，其特征是胰岛自身抗体阳性。因此，诱导B细胞活化的T辅助细胞应答可能在疾病过程中起关键作用。在这里，我们的目的是评估最近描述的一个子集，即C-X-C基序趋化因子受体5型阴性、程序性细胞死亡蛋白1阳性（CXCR 5（-）PD-1（hi））外周T辅助细胞（Tph）细胞在人类1型糖尿病中的作用。方法采用多色流式细胞术分析CXCR 5（-）PD-1（hi）CD 4（+）T细胞表型。在44名新诊断的1型糖尿病儿童，40名自身抗体阳性（AAb（+））高危儿童和84名自身抗体阴性健康对照儿童的队列中分析了循环CXCR 5（-）PD-1（hi）T细胞的频率，并在15名新诊断的1型糖尿病儿童和15名健康对照儿童的单独队列中复制了这些发现。结果循环中CXCR 5（-）PD-1（hi）Tph细胞与循环中CXCR 5（+）PD-1（hi）滤泡性T辅助细胞（Tfh）具有与B细胞辅助功能相关的几个特征。此外，在新诊断的1型糖尿病儿童中，循环Tph细胞的频率增加，特别是在多种自身抗体阳性的儿童中。重要的是，循环Tph细胞也在后来进展为1型糖尿病的自身抗体阳性高危儿童中增加。结论/解释我们的结果表明循环中CXCR 5（-）PD-1（hi）Tph细胞与临床1型糖尿病的进展相关。因此，Tph细胞可能具有作为疾病进展的生物标志物和作为1型糖尿病免疫治疗靶点的潜力。
Aims/hypothesis Type 1 diabetes is preceded by a period of asymptomatic autoimmunity characterised by positivity for islet autoantibodies. Therefore, T helper cell responses that induce B cell activation are likely to play a critical role in the disease process. Here, we aimed to evaluate the role of a recently described subset, C-X-C motif chemokine receptor type 5-negative, programmed cell death protein 1-positive (CXCR5(-)PD-1(hi)) peripheral T helper (Tph) cells, in human type 1 diabetes. Methods The phenotype of blood CXCR5(-)PD-1(hi) CD4(+) T cells was analysed by multicolour flow cytometry. The frequencies of circulating CXCR5(-)PD-1(hi) T cells were analysed in a cohort of 44 children with newly diagnosed type 1 diabetes, 40 autoantibody-positive (AAb(+)) at-risk children and 84 autoantibody-negative healthy control children, and the findings were replicated in a separate cohort of 15 children with newly diagnosed type 1 diabetes and 15 healthy control children. Results Circulating CXCR5(-)PD-1(hi) Tph cells share several features associated with B cell helper function with circulating CXCR5(+)PD-1(hi) follicular T helper (Tfh) cells. Moreover, the frequency of circulating Tph cells was increased in children with newly diagnosed type 1 diabetes, especially in those who are positive for multiple autoantibodies. Importantly, circulating Tph cells were also increased in autoantibody-positive at-risk children who later progressed to type 1 diabetes. Conclusions/interpretation Our results demonstrate that circulating CXCR5(-)PD-1(hi) Tph cells are associated with progression to clinical type 1 diabetes. Consequently, Tph cells could have potential both as a biomarker of disease progression and as a target for immunotherapy in type 1 diabetes.