1 型糖尿病会削弱单次急性运动过程中高度分化的 CD8+T 细胞的动员。
Type 1 diabetes impairs the mobilisation of highly-differentiated CD8+T cells during a single bout of acute exercise.
机构信息
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.Drug Safety and Metabolism, Pathology, AstraZeneca, Cambridge, UK.Department of Surgery, University of Cambridge, Cambridge, UK.
Department for Health, University of Bath, Bath, UK.
出版信息
Exerc Immunol Rev. 2019;25:64-82.
Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that targets and destroys insulin-secreting pancreatic beta cells. Beta cell specific T cells are highly differentiated and show evidence of previous antigen exposure. Exerciseinduced mobilisation of highly-differentiated CD8+ T cells facilitates immune surveillance and regulation. We aimed to explore exercise-induced T cell mobilisation in T1D. In this study, we compared the effects of a single bout of vigorous intensity exercise on T cell mobilisation in T1D and control participants. N=12 T1D (mean age 33.2yrs, predicted VO2 max 32.2 mL/(kg·min), BMI 25.3Kg/m2) and N=12 control (mean age 29.4yrs, predicted VO2 max 38.5mL(kg.min), BMI 23.7Kg/m2) male participants completed a 30-minute bout of cycling at 80% predicted VO2 max in a fasted state. Peripheral blood was collected at baseline, immediately post-exercise, and 1 hour post-exercise. Exercise-induced mobilisation was observed for T cells in both T1D and control groups. Total CD8+ T cells mobilised to a similar extent in T1D (42.7%; p=0.016) and controls (39.7%; p=0.001). CD8 effector memory CD45RA+ (EMRA) subset were the only T cell lineage subset to be significantly mobilised in both groups though the percentage increase of CD8+ EMRA was blunted in T1D (T1D (26.5%) p=0.004, control (66.1%) p=0.010). Further phenotyping of these subsets revealed that the blunting was most evident in CD8+ EMRA that expressed adhesion (CD11b: T1D 37.70%, Control 91.48%) and activation markers (CD69: T1D 29.87%, Control 161.43%), and appeared to be the most differentiated (CD27-CD28-: T1D 7.12%, Control 113.76%). CD4+ T cells mobilised during vigorous intensity exercise in controls (p=0.001), but not in T1D. The blunted mobilisation response of particular T cell subsets was not due to CMV serostatus or apparent differences in exertion during the exercise bout as defined by heart rate and RPE. Predicted VO2 max showed a trend to be lower in the T1D group than the control group but is unlikely to contribute to this blunted response. We postulate the reasons for a blunted mobilisation of differentiated CD8+ EMRA cells includes differences in blood glucose, adrenaline receptor density, and sequestration of T cells in the pancreas of T1D participants. In conclusion, mobilisation of CD8+ EMRA and CD4+ subsets T cells is decreased in people with T1D during acute exercise.
1 型糖尿病（T1D）是一种 T 细胞介导的自身免疫性疾病，其靶向并破坏胰岛β细胞分泌胰岛素。β细胞特异性 T 细胞高度分化，并显示出先前抗原暴露的证据。运动引起的高度分化的 CD8+T 细胞的动员有助于免疫监视和调节。我们旨在探讨 T1D 中运动引起的 T 细胞动员。在这项研究中，我们比较了剧烈强度运动对 T1D 和对照组参与者 T 细胞动员的影响。N=12 例 T1D（平均年龄 33.2 岁，预测 VO2 max 为 32.2 mL/（kg·min），BMI 为 25.3kg/m2）和 N=12 例对照组（平均年龄 29.4 岁，预测 VO2 max 为 38.5mL/（kg·min），BMI 为 23.7kg/m2）男性参与者在禁食状态下以 80%预测 VO2 max 进行 30 分钟的骑行。在基线、运动后即刻和运动后 1 小时采集外周血。在 T1D 和对照组中均观察到 T 细胞的运动诱导动员。T1D（42.7%；p=0.016）和对照组（39.7%；p=0.001）中 CD8+T 细胞动员到相似程度。只有 CD8 效应记忆 CD45RA+（EMRA）亚群在两组中均显著动员，尽管 T1D 中 CD8+EMRA 的百分比增加受到抑制（T1D（26.5%）p=0.004，对照组（66.1%）p=0.010）。对这些亚群的进一步表型分析表明，这种抑制在表达粘附（CD11b：T1D 37.70%，对照 91.48%）和激活标志物（CD69：T1D 29.87%，对照 161.43%）的 CD8+EMRA 中最为明显，并且似乎是最分化的（CD27-CD28-：T1D 7.12%，对照 113.76%）。在对照组中，剧烈强度运动期间 CD4+T 细胞动员（p=0.001），但 T1D 中没有。特定 T 细胞亚群动员反应迟钝的原因不是由于巨细胞病毒血清阳性状态，或在运动期间根据心率和 RPE 定义的明显运动差异。预测的 VO2 max 在 T1D 组中显示出低于对照组的趋势，但不太可能导致这种反应迟钝。我们推测，在 T1D 参与者中，血糖、肾上腺素受体密度和 T 细胞在胰腺中的隔离导致分化的 CD8+EMRA 细胞动员减少。总之，在急性运动期间，T1D 患者的 CD8+EMRA 和 CD4+T 细胞亚群的动员减少。
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