Functional defects and the influence of age on the frequency of CD4+ CD25+ T-cells in type 1 diabetes.

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-1beta, IL-6, IL-8, IL-12p70, and tumor necrosis factor-alpha) 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.