Background: Type 1 diabetes (T1D) is an autoimmune disease resulting from an attack by autoreactive T lymphocytes against pancreatic islet β- cells. In recent studies, regulatory T cells (Tregs) have been implicated in the process of T1D. Furthermore, cluster of differentiation 39 (CD39), which is involved in the suppression of inflammation, has been shown to be expressed on Tregs. However, the pathological importance of CD39 to the memory Treg population remains unclear.
Methods: This study investigated Treg subsets, focusing on resting, effector, and memory Tregs, and determined CD39 expression on Tregs. In addition, changes in Treg subsets and Treg-associated cytokine secretion after CD3/CD28 stimulation of peripheral blood mononuclear cells were evaluated in diabetic patients and healthy controls. The suppressive function of Tregs was measured using the mixed lymphocyte reaction (MLR) test.
Results: There was a higher percentage of memory Tregs in T1D patients than healthy controls. However, Tregs in T1D patients showed impaired suppression, with low forkhead box P3 (Foxp3) expression and low serum interleukin (IL)-10 levels. Furthermore, CD39 expression on Tregs, and on memory Tregs in particular, was lower in T1D patients than healthy controls. After stimulation, the percentage of resting Tregs was decreased and that of effector/memory Tregs was increased in both healthy controls and T1D patients, but CD39 expression on effector/memory Tregs was still lower and there was no increase in IL-10 secretion in T1D patients.
Conclusions: The defective suppressive function of Tregs in T1D patients is due to lower expression of CD39 on memory Tregs.
摘要: 背景 1型糖尿病是一种由自身T淋巴细胞攻击胰岛β细胞而造成的自身免疫性疾病。最近有研究表明调节性T细胞(regulatory T cells，Tregs)在1型糖尿病发病过程中发挥作用，此外也有研究证明分化抗原簇39(CD39)参与炎症抑制过程，且在Tregs上表达。然而，CD39在记忆型Treg亚群中病理学上的重要性仍未阐明。 方法 该研究将分析Tregs亚群，包括静息、效应和记忆Tregs亚群，检测CD39是否在这些Tregs亚群中表达。在患者和健康对照者中，以CD3/CD28刺激外周血单核细胞，观察Tregs亚群及Treg相关细胞因子分泌情况的变化。同时，在混合淋巴细胞反应中检测患者和健康对照Treg的抑制功能。 结果 虽然该研究发现1型糖尿病患者中记忆型Treg亚群比例高于健康对照，但是，1型糖尿病患者Treg的抑制功能受损，同时其Foxp3的表达降低及血清中IL-10分泌水平降低，并且CD39在Tregs中的表达，尤其是在记忆Tregs中的表达低于健康对照。在CD3/CD28磁珠刺激后，不管是患者还是健康对照，静息Treg亚群的比例降低，效应/记忆Treg亚群升高。但是1型糖尿病患者中，PBMCs经过刺激后，CD39在效应/记忆Treg亚群中仍然维持低表达，而IL-10的分泌也并没有上升。 结论 1型糖尿病患者中Treg抑制功能的受损是由于CD39在记忆Treg亚群中的表达降低所致。.
Keywords: 1型糖尿病; CD39; effector/memory; regulatory T cells; type 1 diabetes; 效应/记忆; 调节性T细胞.
© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.