Hamari S, Kirveskoski T, Glumoff V, Kulmala P, Simell O, Knip M, Veijola R
Department of Pediatrics, Medical Research Center Oulu, PEDEGO Research Unit, Oulu University Hospital and University of Oulu, Oulu, Finland.
Research Unit of Biomedicine, University of Oulu, Oulu, Finland.
Scand J Immunol. 2016 Apr;83(4):279-87. doi: 10.1111/sji.12418.
Our aim was to study whether the aberrant amount or function of regulatory T cells is related to the development of type 1 diabetes (T1D) in children. We also set out to investigate the balance of different T cell subtype markers during the T1D autoimmune process. Treg cells were quantified with flow cytometric assay, and the suppression capacity was analysed with a carboxyfluorescein succinimidyl ester (CFSE)-based T cell suppression assay in children in various phases of T1D disease process and in healthy autoantibody-negative control children. The mRNA expression of different T cell subpopulation markers was analysed with real-time qPCR method. The proportion and suppression capacity of regulatory T cells were similar in seroconverted children at an early stage of beta cell autoimmunity and also in children with T1D when compared to healthy and autoantibody-negative children. Significant differences were observed in the mRNA expression of different T cell subpopulation markers in prediabetic children with multiple (≥ 2) autoantibodies and in children with newly diagnosed T1D when compared to the control children. In conclusion, there were no quantitative or functional differences in regulatory T cells between the case and control groups in any phase of the autoimmune process. Decreased mRNA expression levels of T cell subtype markers were observed in children with multiple islet autoantibodies and in those with newly diagnosed T1D, probably reflecting an exhaustion of the immune system after the strong immune activation during the autoimmune process or a generally aberrant immune response related to the progression of the disease.
我们的目的是研究调节性T细胞数量异常或功能异常是否与儿童1型糖尿病(T1D)的发生有关。我们还着手研究T1D自身免疫过程中不同T细胞亚型标志物的平衡情况。采用流式细胞术对调节性T细胞进行定量,并通过基于羧基荧光素琥珀酰亚胺酯(CFSE)的T细胞抑制试验,对处于T1D疾病不同阶段的儿童以及健康的自身抗体阴性对照儿童的调节性T细胞抑制能力进行分析。采用实时定量PCR方法分析不同T细胞亚群标志物的mRNA表达。与健康和自身抗体阴性儿童相比,β细胞自身免疫早期血清转化的儿童以及T1D儿童中调节性T细胞的比例和抑制能力相似。与对照儿童相比,在患有多种(≥2种)自身抗体的糖尿病前期儿童和新诊断的T1D儿童中,观察到不同T细胞亚群标志物的mRNA表达存在显著差异。总之,在自身免疫过程的任何阶段,病例组和对照组之间调节性T细胞在数量或功能上均无差异。在患有多种胰岛自身抗体的儿童和新诊断的T1D儿童中,观察到T细胞亚型标志物的mRNA表达水平降低,这可能反映了自身免疫过程中强烈免疫激活后免疫系统的耗竭,或者与疾病进展相关的普遍异常免疫反应。