Functional defects and the influence of age on the frequency of CD4+CD25+ T-Cells in type 1 diabetes
Functional defects and the influence of age on the frequency of CD4+CD25+ T-Cells in type 1 diabetes
复制标题
DOI：
10.2337/diabetes.54.5.1407
复制
发表时间：
2005-05-01
期刊：
影响因子：
7.7
通讯作者：
Atkinson, MA
中科院分区：
文献类型：
--
作者：
Brusko, TM;Wasserfall, CH;Atkinson, MA
CD4(+)CD25(+) T细胞似乎在调节免疫反应中发挥着至关重要的作用。因此，我们评估了70名1型糖尿病患者和37名健康个体的外周血CD4(+) CD25(+) T细胞频率和功能。有趣的是，在两个受试者组中都观察到年龄增长与CD4(+)CD25(+) T 细胞频率呈正相关。与之前对非肥胖糖尿病小鼠和 1 型糖尿病患者的研究相比，在健康对照受试者和年龄相近的 1 型糖尿病患者中观察到 CD4(+)CD25(+) 和 CD4(+)CD25(+Bright) T 细胞的频率相似。新近发病的 1 型糖尿病受试者与已确诊的 1 型糖尿病受试者在 CD4(+)CD25(+) 或 CD4(+)CD25(+Bright) T 细胞频率方面没有差异。然而，1 型糖尿病患者在体外抑制自体效应 T 细胞增殖的能力明显有缺陷。这种与 1 型糖尿病相关的抑制缺陷与白细胞介素 (IL)-2、γ-干扰素和转化生长因子-β 的产生减少有关，而其他细胞因子，包括适应性和先天免疫细胞因子（IL-10、IL-1β、IL-6、IL-8、IL-12p70 和肿瘤坏死因子-a）在对照受试者中相似 和1型糖尿病患者。这些数据表明，年龄强烈影响CD4(+)CD25(+) T细胞的频率，并且功能而不是频率可能代表这些细胞与人类1型糖尿病相关的方式。
CD4(+)CD25(+) T-cells appear to play a crucial role in regulating the immune response. Therefore, we evaluated the peripheral blood frequency and function of CD4(+) CD25(+) T-cells in 70 type 1 diabetic patients and 37 healthy individuals. Interestingly, a positive correlation was observed between increasing age and CD4(+)CD25(+) T-cell frequency in both subject groups. In contrast to previous studies of nonobese diabetic mice and type 1 diabetic patients, similar frequencies of CD4(+)CD25(+) and CD4(+)CD25(+Bright) T-cells were observed in healthy control subjects and type 1 diabetic patients of similar age. There was no difference between type 1 diabetic subjects of recent-onset versus those with established disease in terms of their CD4(+)CD25(+) or CD4(+)CD25(+Bright) T-cell frequency. However, type 1 diabetic patients were markedly defective in their ability to suppress the proliferation of autologous effector T-cells in vitro. This type 1 diabetes-associated defect in suppression was associated with reduced production of interleukin (IL)-2, gamma-interferon, and transforming growth factor-beta, whereas other cytokines including those of adaptive and innate immunity (IL-10, IL-1 beta, IL-6, IL-8, IL-12p70, and tumor necrosis factor-a) were similar in control subjects and type 1 diabetic patients. These data suggest that age strongly influences the frequency of CD4(+)CD25(+) T-cells and that function, rather than frequency, may represent the means by which these cells associate with type 1 diabetes in humans.