Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, FIN-70210, Kuopio, Finland.
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Diabetologia. 2019 Sep;62(9):1681-1688. doi: 10.1007/s00125-019-4936-8. Epub 2019 Jul 3.
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 (CXCR5PD-1) peripheral T helper (Tph) cells, in human type 1 diabetes.
The phenotype of blood CXCR5PD-1 CD4 T cells was analysed by multicolour flow cytometry. The frequencies of circulating CXCR5PD-1 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.
Circulating CXCR5PD-1 Tph cells share several features associated with B cell helper function with circulating CXCR5PD-1 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 CXCR5PD-1 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.
目的/假设：1 型糖尿病之前存在一段无症状自身免疫期，其特征是胰岛自身抗体阳性。因此，诱导 B 细胞活化的辅助性 T 细胞反应可能在疾病过程中发挥关键作用。在这里，我们旨在评估最近描述的一个亚群，即 C-X-C 基序趋化因子受体 5 阴性、程序性细胞死亡蛋白 1 阳性（CXCR5PD-1）外周辅助性 T（Tph）细胞在人类 1 型糖尿病中的作用。
通过多色流式细胞术分析血液 CXCR5PD-1 CD4 T 细胞的表型。分析了 44 名新诊断为 1 型糖尿病的儿童、40 名自身抗体阳性（AAb）的高危儿童和 84 名自身抗体阴性的健康对照儿童的循环 CXCR5PD-1 T 细胞的频率，并在另一组 15 名新诊断为 1 型糖尿病和 15 名健康对照儿童中进行了复制。
循环 CXCR5PD-1 Tph 细胞具有与循环 CXCR5PD-1 滤泡辅助性 T（Tfh）细胞相关的几种与 B 细胞辅助功能相关的特征。此外，新诊断为 1 型糖尿病的儿童中循环 Tph 细胞的频率增加，尤其是那些多种自身抗体阳性的儿童。重要的是，自身抗体阳性的高危儿童中也增加了循环 Tph 细胞，这些儿童后来发展为 1 型糖尿病。
结论/解释：我们的研究结果表明，循环 CXCR5PD-1 Tph 细胞与进展为临床 1 型糖尿病相关。因此，Tph 细胞可能具有作为疾病进展的生物标志物和 1 型糖尿病免疫治疗靶点的潜力。
