Defective suppressor function in CD4+CD25+ T-cells from patients with type 1 diabetes
Defective suppressor function in CD4+CD25+ T-cells from patients with type 1 diabetes
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DOI：
10.2337/diabetes.54.1.92
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发表时间：
2005-01-01
期刊：
影响因子：
7.7
通讯作者：
Tree, TIM
中科院分区：
文献类型：
--
作者：
Lindley, S;Dayan, CM;Tree, TIM
1型糖尿病是一种T细胞介导的疾病，与对自身抗原的免疫耐受性丧失有关。维持外周耐受性的机制包括CD 4（+）CD 25（+）T细胞群中的调节性T细胞（Treg）的特化亚群，但这些细胞在1型糖尿病中的功能和表型尚未研究。我们假设CD 4 + CD 25 + Treg群体或其功能的缺陷可能导致1型糖尿病患者缺乏明显的自身耐受性。我们发现，虽然CD 4 + CD 25 + T细胞的水平是正常的，在最近发生的成人1型糖尿病患者，在体外共培养过程中，TcR在这个群体中抑制T细胞增殖的能力是显着降低与对照组相比（P = 0.007）。此外，在1型糖尿病患者中，这些共培养物显示出更多的促炎表型，干扰素-γ分泌增加（P 0.005），白细胞介素-10产生减少（P = 0.03）。这些缺陷可能反映了CD 4（+）CD 25（+）群体平衡的紊乱，因为在1型糖尿病患者中，这些细胞共表达早期活化标志物CD 69（P = 0.007）和细胞内CTLA-4（P = 0.01）的比例较高。这些数据表明CD 4（+）CD 25（+）Treg群体的功能缺陷可能影响1型糖尿病的发病机制。
Type 1 diabetes is a T-cell-mediated disease that is associated with loss of immunological tolerance to self-antigens. The mechanisms involved in maintenance of peripheral tolerance include a specialized subset of regulatory T-cells (Treg) within the CD4(+)CD25(+) T-cell population, but the function and phenotype of these cells in type 1 diabetes have not been investigated. We hypothesized that a deficiency in the CD4+CD25+ Treg population or its function could contribute to the lack of self-tolerance evident in patients with type 1 diabetes. We show that although levels of CD4+CD25+ T-cells are normal in patients with recent-onset adult type 1 diabetes, the ability of the Tregs in this population to suppress T-cell proliferation during in vitro cocultures is markedly reduced compared with control subjects (P = 0.007). Moreover, in patients with type 1 diabetes, these cocultures display a more proinflammatory phenotype, with increased secretion of interferon-gamma (P 0.005) and decreased interleukin-10 production (P = 0.03). These deficiencies may reflect a disturbance in the balance of the CD4(+)CD25(+) population, because in patients with type 1 diabetes, a higher proportion of these cells coexpress the early activation marker CD69 (P = 0.007) and intracellular CTLA-4 (P = 0.01). These data demonstrate deficiency in function of the CD4(+)CD25(+) Treg population that may influence the pathogenesis of type 1 diabetes.