Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes.
Evaluation of in vivo T cell kinetics: use of heavy isotope labelling in type 1 diabetes.
复制标题
体内 T 细胞动力学评估：重同位素标记在 1 型糖尿病中的应用。
DOI：
10.1111/cei.12064
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发表时间：
2013
影响因子：
4.6
通讯作者：
Greenbaum,CJ
中科院分区：
文献类型：
--
作者：
Bollyky,JB;Long,SA;Fitch,M;Bollyky,PL;Rieck,M;Rogers,R;Samuels,PL;Sanda,S;Buckner,JH;Hellerstein,MK;Greenbaum,CJ
CD 4+记忆细胞的发育取决于T细胞受体（TCR）信号强度、抗原剂量和细胞因子环境，所有这些在1型糖尿病（T1 D）中都会改变。我们假设1型糖尿病受试者的CD 4 +T细胞周转率高于对照组，T细胞功能的体外研究无法评估免疫细胞稳态的动态方面。因此，我们使用氧化氘（2 H2O）来评估T1 D（n= 10）和对照受试者（n = 10）中CD 4 +T细胞亚群的体内周转。收集幼稚、记忆和调节（Treg）CD 4 +T细胞亚群的系列样品，并通过气相色谱-质谱（GC-MS）测定脱氧核糖的富集。使用数学模型进行T细胞更新的定量以估计富集分数（f，n= 20）、更新速率（k，n= 20）、增殖（p，n= 10）和消失（d*，n= 10）。尽管在对照组和T1 D受试者中，Tregs的更新率都大于记忆和幼稚细胞，但T1 D和对照组之间的Tregor幼稚动力学没有差异。然而，与对照受试者相比，T1 D患者的CD 4+记忆T细胞周转更快。掺入氘的测量和建模对于评估T1 D中免疫细胞的体内动力学是有用的，并且可以被纳入疾病的自然史的研究或旨在改变疾病过程的临床试验。增强的CD 4+记忆T细胞周转T1 D可能是重要的了解自身免疫性糖尿病的病理生理和潜在的治疗。
CD4+memory cell development is dependent upon T cell receptor (TCR) signal strength, antigen dose and the cytokine milieu, all of which are altered in type 1 diabetes (T1D). We hypothesized that CD4+T cell turnover would be greater in type 1 diabetes subjects compared to controls.In vitrostudies of T cell function are unable to evaluate dynamic aspects of immune cell homoeostasis. Therefore, we used deuterium oxide (2H2O) to assessin vivoturnover of CD4+T cell subsets in T1D (n= 10) and control subjects (n= 10). Serial samples of naive, memory and regulatory (Treg) CD4+T cell subsets were collected and enrichment of deoxyribose was determined by gas chromatography–mass spectrometry (GC–MS). Quantification of T cell turnover was performed using mathematical models to estimate fractional enrichment (f,n= 20), turnover rate (k,n= 20), proliferation (p,n= 10) and disappearance (d*,n= 10). Although turnover of Tregswas greater than memory and naive cells in both controls and T1D subjects, no differences were seen between T1D and controls in Tregor naive kinetics. However, turnover of CD4+memory T cells was faster in those with T1D compared to control subjects. Measurement and modelling of incorporated deuterium is useful for evaluating thein vivokinetics of immune cells in T1D and could be incorporated into studies of the natural history of disease or clinical trials designed to alter the disease course. The enhanced CD4+memory T cell turnover in T1D may be important in understanding the pathophysiology and potential treatments of autoimmune diabetes.