Functional Defects and the Influence of Age on the Frequency of CD4+CD25+ T-Cells in Type 1 Diabetes

  1. Todd M. Brusko1,
  2. Clive H. Wasserfall1,
  3. Michael J. Clare-Salzler1,
  4. Desmond A. Schatz2 and
  5. Mark A. Atkinson1
  1. 1Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida
  2. 2Department of Pediatrics, University of Florida, Gainesville, Florida
  1. Address correspondence and reprint requests to Mark A. Atkinson, PhD, Department of Pathology, College of Medicine, University of Florida, ARB-R3-128, 1600 SW Archer Rd., Gainesville, FL 32610-0275. E-mail: atkinson{at}


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+BrightT-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, γ-interferon, and transforming growth factor-β, whereas other cytokines including those of adaptive and innate immunity (IL-10, IL-1β, IL-6, IL-8, IL-12p70, and tumor necrosis factor-α) 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.


    • Accepted February 9, 2005.
    • Received October 20, 2004.
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